Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

The Role of Mitochondrial Genes in Neurodegenerative Disorders

Author(s): Rajesh Kumar, Seetha Harilal, Della Grace Thomas Parambi, S.K. Kanthlal, Md Atiar Rahman, Athanasios Alexiou*, Gaber El-Saber Batiha and Bijo Mathew*

Volume 20, Issue 5, 2022

Published on: 14 March, 2022

Page: [824 - 835] Pages: 12

DOI: 10.2174/1570159X19666210908163839

Price: $65

Abstract

Mitochondrial disorders are clinically heterogeneous, resulting from nuclear gene and mitochondrial mutations that disturb the mitochondrial functions and dynamics. There is a lack of evidence linking mtDNA mutations to neurodegenerative disorders, mainly due to the absence of noticeable neuropathological lesions in postmortem samples. This review describes various gene mutations in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. These abnormalities, including PINK1, Parkin, and SOD1 mutations, seem to reveal mitochondrial dysfunctions due to either mtDNA mutation or deletion, the mechanism of which remains unclear in depth.

Keywords: Alzheimer's disease, amyotrophic lateral sclerosis, mtDNA, multiple sclerosis, neurodegeneration, Parkinson's disease, stroke.

« Previous Next »
Graphical Abstract

[1]
Keogh, M.J.; Chinnery, P.F. Mitochondrial DNA mutations in neurodegeneration. Biochim. Biophys. Acta, 2015, 1847(11), 1401-1411.
[http://dx.doi.org/10.1016/j.bbabio.2015.05.015] [PMID: 26014345]
[2]
Trounce, I.; Byrne, E.; Marzuki, S. Decline in skeletal muscle mitochondrial respiratory chain function: Possible factor in ageing. Lancet, 1989, 1(8639), 637-639.
[http://dx.doi.org/10.1016/S0140-6736(89)92143-0] [PMID: 2564459]
[3]
Bender, A.; Krishnan, K.J.; Morris, C.M.; Taylor, G.A.; Reeve, A.K.; Perry, R.H.; Jaros, E.; Hersheson, J.S.; Betts, J.; Klopstock, T.; Taylor, R.W.; Turnbull, D.M. High levels of mitochondrial DNA deletions in Substantia nigra neurons in aging and Parkinson disease. Nat. Genet., 2006, 38(5), 515-517.
[http://dx.doi.org/10.1038/ng1769] [PMID: 16604074]
[4]
van der Giezen, M.; Tovar, J. Degenerate mitochondria. EMBO Rep., 2005, 6(6), 525-530.
[http://dx.doi.org/10.1038/sj.embor.7400440] [PMID: 15940286]
[5]
Celsi, F.; Pizzo, P.; Brini, M.; Leo, S.; Fotino, C.; Pinton, P.; Rizzuto, R. Mitochondria, calcium and cell death: A deadly triad in neurodegeneration. Biochim. Biophys. Acta, 2009, 1787(5), 335-344.
[http://dx.doi.org/10.1016/j.bbabio.2009.02.021] [PMID: 19268425]
[6]
Bossy-Wetzel, E.; Barsoum, M.J.; Godzik, A.; Schwarzenbacher, R.; Lipton, S.A. Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr. Opin. Cell Biol., 2003, 15(6), 706-716.
[http://dx.doi.org/10.1016/j.ceb.2003.10.015] [PMID: 14644195]
[7]
Ross, J.M.; Stewart, J.B.; Hagström, E.; Brené, S.; Mourier, A.; Coppotelli, G.; Freyer, C.; Lagouge, M.; Hoffer, B.J.; Olson, L.; Larsson, N.G. Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature, 2013, 501(7467), 412-415.
[http://dx.doi.org/10.1038/nature12474] [PMID: 23965628]
[8]
Monzio Compagnoni, G.; Di Fonzo, A.; Corti, S.; Comi, G.P.; Bresolin, N.; Masliah, E. The role of mitochondria in neurodegenerative diseases: the lesson from Alzheimer’s disease and Parkinson’s disease. Mol. Neurobiol., 2020, 57(7), 2959-2980.
[http://dx.doi.org/10.1007/s12035-020-01926-1] [PMID: 32445085]
[9]
Turnbull, H.E.; Lax, N.Z.; Diodato, D.; Ansorge, O.; Turnbull, D.M. The mitochondrial brain: From mitochondrial genome to neurodegeneration. Biochim. Biophys. Acta, 2010, 1802(1), 111-121.
[http://dx.doi.org/10.1016/j.bbadis.2009.07.010] [PMID: 19647794]
[10]
Wright, A.F.; Murphy, M.P.; Turnbull, D.M. Do organellar genomes function as long-term redox damage sensors? Trends Genet., 2009, 25(6), 253-261.
[http://dx.doi.org/10.1016/j.tig.2009.04.006] [PMID: 19481287]
[11]
Ruiz-Pesini, E.; Lott, M.T.; Procaccio, V.; Poole, J.C.; Brandon, M.C.; Mishmar, D.; Yi, C.; Kreuziger, J.; Baldi, P.; Wallace, D.C. An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res., 2007, 35(Database issue)(Suppl. 1), D823-D828.
[http://dx.doi.org/10.1093/nar/gkl927] [PMID: 17178747]
[12]
Simcox, E.M.; Reeve, A.K. An introduction to mitochondria, their structure and functions.Mitochondrial Dysfunction in Neurodegenerative Disorders; Springer, 2016, pp. 3-30.
[http://dx.doi.org/10.1007/978-3-319-28637-2_1]
[13]
Li, H.; Liu, D.; Lu, J.; Bai, Y. Physiology and pathophysiology of mitochondrial DNA. Advances in Mitochondrial Medicine; Springer, 2012, pp. 39-51.
[http://dx.doi.org/10.1007/978-94-007-2869-1_2]
[14]
Hudson, G.; Amati-Bonneau, P.; Blakely, E.L.; Stewart, J.D.; He, L.; Schaefer, A.M.; Griffiths, P.G.; Ahlqvist, K.; Suomalainen, A.; Reynier, P.; McFarland, R.; Turnbull, D.M.; Chinnery, P.F.; Taylor, R.W. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: A novel disorder of mtDNA maintenance. Brain, 2008, 131(Pt 2), 329-337.
[http://dx.doi.org/10.1093/brain/awm272] [PMID: 18065439]
[15]
Bogenhagen, D.F. Mitochondrial DNA nucleoid structure. Biochim. Biophys. Acta, 2012, 1819(9-10), 914-920.
[http://dx.doi.org/10.1016/j.bbagrm.2011.11.005] [PMID: 22142616]
[16]
Bobba, K.N.; Binoy, A.; Koo, S.; Nedungadi, D.; Podder, A.; Sharma, A.; Mishra, N.; Kim, J.S.; Bhuniya, S. Direct readout protonophore induced selective uncoupling and dysfunction of individual mitochondria within cancer cells. Chem. Commun. (Camb.), 2019, 55(45), 6429-6432.
[http://dx.doi.org/10.1039/C9CC01483G] [PMID: 31094377]
[17]
Anderson, S.; Bankier, A.T.; Barrell, B.G.; de Bruijn, M.H.; Coulson, A.R.; Drouin, J.; Eperon, I.C.; Nierlich, D.P.; Roe, B.A.; Sanger, F.; Schreier, P.H.; Smith, A.J.; Staden, R.; Young, I.G. Sequence and organization of the human mitochondrial genome. Nature, 1981, 290(5806), 457-465.
[http://dx.doi.org/10.1038/290457a0] [PMID: 7219534]
[18]
Andrews, R.M.; Kubacka, I.; Chinnery, P.F.; Lightowlers, R.N.; Turnbull, D.M.; Howell, N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet., 1999, 23(2), 147-147.
[http://dx.doi.org/10.1038/13779] [PMID: 10508508]
[19]
Wiesner, R.J.; Rüegg, J.C.; Morano, I. Counting target molecules by exponential polymerase chain reaction: Copy number of mitochondrial DNA in rat tissues. Biochem. Biophys. Res. Commun., 1992, 183(2), 553-559.
[http://dx.doi.org/10.1016/0006-291X(92)90517-O] [PMID: 1550563]
[20]
Clayton, D.A. Replication of animal mitochondrial DNA. Cell, 1982, 28(4), 693-705.
[http://dx.doi.org/10.1016/0092-8674(82)90049-6] [PMID: 6178513]
[21]
Holt, I.J.; Lorimer, H.E.; Jacobs, H.T. Coupled leading- and lagging-strand synthesis of mammalian mitochondrial DNA. Cell, 2000, 100(5), 515-524.
[http://dx.doi.org/10.1016/S0092-8674(00)80688-1] [PMID: 10721989]
[22]
Scarpulla, R.C. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol. Rev., 2008, 88(2), 611-638.
[http://dx.doi.org/10.1152/physrev.00025.2007] [PMID: 18391175]
[23]
Rorbach, J.; Soleimanpour-Lichaei, R.; Lightowlers, R.N.; Chrzanowska-Lightowlers, Z.M.A. How do mammalian mitochondria synthesize proteins?; Portland Press Ltd., 2007.
[http://dx.doi.org/10.1042/BST0351290]
[24]
Liao, H-X.; Spremulli, L.L. Initiation of protein synthesis in animal mitochondria. Purification and characterization of translational initiation factor 2. J. Biol. Chem., 1991, 266(31), 20714-20719.
[http://dx.doi.org/10.1016/S0021-9258(18)54767-0] [PMID: 1939122]
[25]
Schwartzbach, C.J.; Spremulli, L.L. Bovine mitochondrial protein synthesis elongation factors. Identification and initial characterization of an elongation factor Tu-elongation factor Ts complex. J. Biol. Chem., 1989, 264(32), 19125-19131.
[http://dx.doi.org/10.1016/S0021-9258(19)47276-1] [PMID: 2808417]
[26]
Soleimanpour-Lichaei, H.R.; Kühl, I.; Gaisne, M.; Passos, J.F.; Wydro, M.; Rorbach, J.; Temperley, R.; Bonnefoy, N.; Tate, W.; Lightowlers, R.; Chrzanowska-Lightowlers, Z. mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol. Cell, 2007, 27(5), 745-757.
[http://dx.doi.org/10.1016/j.molcel.2007.06.031] [PMID: 17803939]
[27]
Brandon, M.C.; Lott, M.T.; Nguyen, K.C.; Spolim, S.; Navathe, S.B.; Baldi, P.; Wallace, D.C. MITOMAP: A human mitochondrial genome database--2004 update. Nucleic Acids Res., 2005, 33(Database issue)(Suppl. 1), D611-D613.
[http://dx.doi.org/10.1093/nar/gki079] [PMID: 15608272]
[28]
Tuppen, H.A.; Blakely, E.L.; Turnbull, D.M.; Taylor, R.W. Mitochondrial DNA mutations and human disease. Biochim. Biophys. Acta, 2010, 1797(2), 113-128.
[http://dx.doi.org/10.1016/j.bbabio.2009.09.005] [PMID: 19761752]
[29]
Taylor, R.W.; Turnbull, D.M. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet., 2005, 6(5), 389-402.
[http://dx.doi.org/10.1038/nrg1606] [PMID: 15861210]
[30]
van Oven, M.; Kayser, M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum. Mutat., 2009, 30(2), E386-E394.
[http://dx.doi.org/10.1002/humu.20921] [PMID: 18853457]
[31]
Sigurğardóttir, S.; Helgason, A.; Gulcher, J.R.; Stefansson, K.; Donnelly, P. The mutation rate in the human mtDNA control region. Am. J. Hum. Genet., 2000, 66(5), 1599-1609.
[http://dx.doi.org/10.1086/302902] [PMID: 10756141]
[32]
Torroni, A.; Schurr, T.G.; Cabell, M.F.; Brown, M.D.; Neel, J.V.; Larsen, M.; Smith, D.G.; Vullo, C.M.; Wallace, D.C. Asian affinities and continental radiation of the four founding Native American mtDNAs. Am. J. Hum. Genet., 1993, 53(3), 563-590.
[PMID: 7688932]
[33]
Richards, M.B.; Macaulay, V.A.; Bandelt, H-J.; Sykes, B.C. Phylogeography of mitochondrial DNA in western Europe. Ann. Hum. Genet., 1998, 62(Pt 3), 241-260.
[http://dx.doi.org/10.1046/j.1469-1809.1998.6230241.x] [PMID: 9803269]
[34]
Mancuso, M.; Nardini, M.; Micheli, D.; Rocchi, A.; Nesti, C.; Giglioli, N.J.; Petrozzi, L.; Rossi, C.; Ceravolo, R.; Bacci, A.; Choub, A.; Ricci, G.; Tognoni, G.; Manca, M.L.; Siciliano, G.; Murri, L. Lack of association between mtDNA haplogroups and Alzheimer’s disease in Tuscany. Neurol. Sci., 2007, 28(3), 142-147.
[http://dx.doi.org/10.1007/s10072-007-0807-z] [PMID: 17603766]
[35]
Lakatos, A.; Derbeneva, O.; Younes, D.; Keator, D.; Bakken, T.; Lvova, M.; Brandon, M.; Guffanti, G.; Reglodi, D.; Saykin, A.; Weiner, M.; Macciardi, F.; Schork, N.; Wallace, D.C.; Potkin, S.G. Association between mitochondrial DNA variations and Alzheimer’s disease in the ADNI cohort. Neurobiol. Aging, 2010, 31(8), 1355-1363.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.031] [PMID: 20538375]
[36]
Ridge, P.G.; Maxwell, T.J.; Corcoran, C.D.; Norton, M.C.; Tschanz, J.T.; O’Brien, E.; Kerber, R.A.; Cawthon, R.M.; Munger, R.G.; Kauwe, J.S. Mitochondrial genomic analysis of late onset Alzheimer’s disease reveals protective haplogroups H6A1A/H6A1B: The Cache County Study on Memory in Aging. PLoS One, 2012, 7(9), e45134.
[http://dx.doi.org/10.1371/journal.pone.0045134] [PMID: 23028804]
[37]
Mehta, P.; Mellick, G.D.; Rowe, D.B.; Halliday, G.M.; Jones, M.M.; Manwaring, N.; Vandebona, H.; Silburn, P.A.; Wang, J.J.; Mitchell, P.; Sue, C.M. Mitochondrial DNA haplogroups J and K are not protective for Parkinson’s disease in the Australian community. Mov. Disord., 2009, 24(2), 290-292.
[http://dx.doi.org/10.1002/mds.22389] [PMID: 19086081]
[38]
Latsoudis, H.; Spanaki, C.; Chlouverakis, G.; Plaitakis, A. Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background. J. Hum. Genet., 2008, 53(4), 349-356.
[http://dx.doi.org/10.1007/s10038-008-0259-1] [PMID: 18286226]
[39]
Ghezzi, D.; Marelli, C.; Achilli, A.; Goldwurm, S.; Pezzoli, G.; Barone, P.; Pellecchia, M.T.; Stanzione, P.; Brusa, L.; Bentivoglio, A.R.; Bonuccelli, U.; Petrozzi, L.; Abbruzzese, G.; Marchese, R.; Cortelli, P.; Grimaldi, D.; Martinelli, P.; Ferrarese, C.; Garavaglia, B.; Sangiorgi, S.; Carelli, V.; Torroni, A.; Albanese, A.; Zeviani, M. Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson’s disease in Italians. Eur. J. Hum. Genet., 2005, 13(6), 748-752.
[http://dx.doi.org/10.1038/sj.ejhg.5201425] [PMID: 15827561]
[40]
Ingram, C.J.; Weale, M.E.; Plaster, C.A.; Morrison, K.E.; Goodall, E.F.; Pall, H.S.; Beck, M.; Jablonka, S.; Sendtner, M.; Fisher, E.M.; Bradman, N.; Kasperavičiūtė, D. Analysis of European case-control studies suggests that common inherited variation in mitochondrial DNA is not involved in susceptibility to amyotrophic lateral sclerosis. Amyotroph. Lateral Scler., 2012, 13(4), 341-346.
[http://dx.doi.org/10.3109/17482968.2012.654394] [PMID: 22409358]
[41]
Chinnery, P.F.; Elliott, H.R.; Syed, A.; Rothwell, P.M. Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: A genetic association study. Lancet Neurol., 2010, 9(5), 498-503.
[http://dx.doi.org/10.1016/S1474-4422(10)70083-1] [PMID: 20362514]
[42]
Rose, G.; Longo, T.; Maletta, R.; Passarino, G.; Bruni, A.C.; De Benedictis, G. No evidence of association between frontotemporal dementia and major European mtDNA haplogroups. Eur. J. Neurol., 2008, 15(9), 1006-1008.
[http://dx.doi.org/10.1111/j.1468-1331.2008.02222.x] [PMID: 18637035]
[43]
Caldecott, K.W. Single-strand break repair and genetic disease. Nat. Rev. Genet., 2008, 9(8), 619-631.
[http://dx.doi.org/10.1038/nrg2380] [PMID: 18626472]
[44]
Spelbrink, J.N.; Van Oost, B.A.; Van den Bogert, C. The relationship between mitochondrial genotype and mitochondrial phenotype in lymphoblasts with a heteroplasmic mtDNA deletion. Hum. Mol. Genet., 1994, 3(11), 1989-1997.
[http://dx.doi.org/10.1093/hmg/3.11.1989] [PMID: 7874116]
[45]
Baines, H.L.; Stewart, J.B.; Stamp, C.; Zupanic, A.; Kirkwood, T.B.; Larsson, N-G.; Turnbull, D.M.; Greaves, L.C. Similar patterns of clonally expanded somatic mtDNA mutations in the colon of heterozygous mtDNA mutator mice and ageing humans. Mech. Ageing Dev., 2014, 139, 22-30.
[http://dx.doi.org/10.1016/j.mad.2014.06.003] [PMID: 24915468]
[46]
Trifunovic, A.; Wredenberg, A.; Falkenberg, M.; Spelbrink, J.N.; Rovio, A.T.; Bruder, C.E.; Bohlooly-Y, M.; Gidlöf, S.; Oldfors, A.; Wibom, R.; Törnell, J.; Jacobs, H.T.; Larsson, N.G. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 2004, 429(6990), 417-423.
[http://dx.doi.org/10.1038/nature02517] [PMID: 15164064]
[47]
Stewart, J.B.; Freyer, C.; Elson, J.L.; Wredenberg, A.; Cansu, Z.; Trifunovic, A.; Larsson, N.G. Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol., 2008, 6(1), e10.
[http://dx.doi.org/10.1371/journal.pbio.0060010] [PMID: 18232733]
[48]
Rossi, M.N.; Carbone, M.; Mostocotto, C.; Mancone, C.; Tripodi, M.; Maione, R.; Amati, P. Mitochondrial localization of PARP-1 requires interaction with mitofilin and is involved in the maintenance of mitochondrial DNA integrity. J. Biol. Chem., 2009, 284(46), 31616-31624.
[http://dx.doi.org/10.1074/jbc.M109.025882] [PMID: 19762472]
[49]
Szczesny, B.; Tann, A.W.; Longley, M.J.; Copeland, W.C.; Mitra, S. Long patch base excision repair in mammalian mitochondrial genomes. J. Biol. Chem., 2008, 283(39), 26349-26356.
[http://dx.doi.org/10.1074/jbc.M803491200] [PMID: 18635552]
[50]
Kleff, S.; Kemper, B.; Sternglanz, R. Identification and characterization of yeast mutants and the gene for a cruciform cutting endonuclease. EMBO J., 1992, 11(2), 699-704.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05102.x] [PMID: 1537343]
[51]
Krishnan, K.J.; Reeve, A.K.; Samuels, D.C.; Chinnery, P.F.; Blackwood, J.K.; Taylor, R.W.; Wanrooij, S.; Spelbrink, J.N.; Lightowlers, R.N.; Turnbull, D.M. What causes mitochondrial DNA deletions in human cells? Nat. Genet., 2008, 40(3), 275-279.
[http://dx.doi.org/10.1038/ng.f.94] [PMID: 18305478]
[52]
Elson, J.L.; Samuels, D.C.; Turnbull, D.M.; Chinnery, P.F. Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am. J. Hum. Genet., 2001, 68(3), 802-806.
[http://dx.doi.org/10.1086/318801] [PMID: 11179029]
[53]
Payne, B.A.; Wilson, I.J.; Yu-Wai-Man, P.; Coxhead, J.; Deehan, D.; Horvath, R.; Taylor, R.W.; Samuels, D.C.; Santibanez-Koref, M.; Chinnery, P.F. Universal heteroplasmy of human mitochondrial DNA. Hum. Mol. Genet., 2013, 22(2), 384-390.
[http://dx.doi.org/10.1093/hmg/dds435] [PMID: 23077218]
[54]
Khrapko, K. The timing of mitochondrial DNA mutations in aging. Nat. Genet., 2011, 43(8), 726-727.
[http://dx.doi.org/10.1038/ng.895] [PMID: 21792237]
[55]
Müller-Höcker, J. Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration. J. Neurol. Sci., 1990, 100(1-2), 14-21.
[http://dx.doi.org/10.1016/0022-510X(90)90006-9] [PMID: 1965203]
[56]
Müller-Höcker, J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart--an age-related phenomenon. A histochemical ultracytochemical study. Am. J. Pathol., 1989, 134(5), 1167-1173.
[PMID: 2541614]
[57]
Fayet, G.; Jansson, M.; Sternberg, D.; Moslemi, A-R.; Blondy, P.; Lombès, A.; Fardeau, M.; Oldfors, A. Ageing muscle: Clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function. Neuromuscul. Disord., 2002, 12(5), 484-493.
[http://dx.doi.org/10.1016/S0960-8966(01)00332-7] [PMID: 12031622]
[58]
Nambiar, J.; Vijayakumar, G.; Drishya, G.; Shaji, S.K.; Pandurangan, N.; Kumar, G.B.; Nair, B.G. (I-3,II-3)-Biacacetin-mediated cell death involves mitochondria. Mol. Cell. Biochem., 2019, 451(1-2), 79-90.
[http://dx.doi.org/10.1007/s11010-018-3395-8] [PMID: 29968167]
[59]
Rossignol, R.; Malgat, M.; Mazat, J-P.; Letellier, T. Threshold effect and tissue specificity. Implication for mitochondrial cytopathies. J. Biol. Chem., 1999, 274(47), 33426-33432.
[http://dx.doi.org/10.1074/jbc.274.47.33426] [PMID: 10559224]
[60]
Boulet, L.; Karpati, G.; Shoubridge, E.A. Distribution and threshold expression of the tRNA(Lys) mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF). Am. J. Hum. Genet., 1992, 51(6), 1187-1200.
[PMID: 1334369]
[61]
Hayashi, J.; Ohta, S.; Kikuchi, A.; Takemitsu, M.; Goto, Y.; Nonaka, I. Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA, 1991, 88(23), 10614-10618.
[http://dx.doi.org/10.1073/pnas.88.23.10614] [PMID: 1720544]
[62]
James, A.M.; Wei, Y.H.; Pang, C.Y.; Murphy, M.P. Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations. Biochem. J., 1996, 318(Pt 2), 401-407.
[http://dx.doi.org/10.1042/bj3180401] [PMID: 8809026]
[63]
D’Aurelio, M.; Pallotti, F.; Barrientos, A.; Gajewski, C.D.; Kwong, J.Q.; Bruno, C.; Beal, M.F.; Manfredi, G. In vivo regulation of oxidative phosphorylation in cells harboring a stop-codon mutation in mitochondrial DNA-encoded cytochrome c oxidase subunit I. J. Biol. Chem., 2001, 276(50), 46925-46932.
[http://dx.doi.org/10.1074/jbc.M106429200] [PMID: 11595737]
[64]
Rossignol, R.; Faustin, B.; Rocher, C.; Malgat, M.; Mazat, J-P.; Letellier, T. Mitochondrial threshold effects. Biochem. J., 2003, 370(Pt 3), 751-762.
[http://dx.doi.org/10.1042/bj20021594] [PMID: 12467494]
[65]
Bai, Y.; Shakeley, R.M.; Attardi, G. Tight control of respiration by NADH dehydrogenase ND5 subunit gene expression in mouse mitochondria. Mol. Cell. Biol., 2000, 20(3), 805-815.
[http://dx.doi.org/10.1128/MCB.20.3.805-815.2000] [PMID: 10629037]
[66]
Enriquez, J.A.; Chomyn, A.; Attardi, G. MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNA(Lys) and premature translation termination. Nat. Genet., 1995, 10(1), 47-55.
[http://dx.doi.org/10.1038/ng0595-47] [PMID: 7647790]
[67]
Cortopassi, G.A.; Shibata, D.; Soong, N.W.; Arnheim, N. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc. Natl. Acad. Sci. USA, 1992, 89(16), 7370-7374.
[http://dx.doi.org/10.1073/pnas.89.16.7370] [PMID: 1502147]
[68]
Corral-Debrinski, M.; Shoffner, J.M.; Lott, M.T.; Wallace, D.C. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat. Res., 1992, 275(3-6), 169-180.
[http://dx.doi.org/10.1016/0921-8734(92)90021-G] [PMID: 1383759]
[69]
Meissner, C.; Bruse, P.; Mohamed, S.A.; Schulz, A.; Warnk, H.; Storm, T.; Oehmichen, M. The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more? Exp. Gerontol., 2008, 43(7), 645-652.
[http://dx.doi.org/10.1016/j.exger.2008.03.004] [PMID: 18439778]
[70]
Corral-Debrinski, M.; Horton, T.; Lott, M.T.; Shoffner, J.M.; Beal, M.F.; Wallace, D.C. Mitochondrial DNA deletions in human brain: Regional variability and increase with advanced age. Nat. Genet., 1992, 2(4), 324-329.
[http://dx.doi.org/10.1038/ng1292-324] [PMID: 1303288]
[71]
Soong, N.W.; Hinton, D.R.; Cortopassi, G.; Arnheim, N. Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain. Nat. Genet., 1992, 2(4), 318-323.
[http://dx.doi.org/10.1038/ng1292-318] [PMID: 1303287]
[72]
Cooper, J.M.; Mann, V.M.; Schapira, A.H.V. Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: Effect of ageing. J. Neurol. Sci., 1992, 113(1), 91-98.
[http://dx.doi.org/10.1016/0022-510X(92)90270-U] [PMID: 1469460]
[73]
Hamblet, N.S.; Castora, F.J. Elevated levels of the Kearns-Sayre syndrome mitochondrial DNA deletion in temporal cortex of Alzheimer’s patients. Mutat. Res., 1997, 379(2), 253-262.
[http://dx.doi.org/10.1016/S0027-5107(97)00158-9] [PMID: 9357554]
[74]
Damas, J.; Samuels, D.C.; Carneiro, J.; Amorim, A.; Pereira, F. Mitochondrial DNA rearrangements in health and disease--a comprehensive study. Hum. Mutat., 2014, 35(1), 1-14.
[http://dx.doi.org/10.1002/humu.22452] [PMID: 24115352]
[75]
Coppedè, F.; Stoccoro, A. Mitoepigenetics and neurodegenerative diseases. Front. Endocrinol. (Lausanne), 2019, 10, 86.
[http://dx.doi.org/10.3389/fendo.2019.00086] [PMID: 30837953]
[76]
Sharma, N.; Pasala, M.S.; Prakash, A. Mitochondrial DNA: Epigenetics and environment. Environ. Mol. Mutagen., 2019, 60(8), 668-682.
[http://dx.doi.org/10.1002/em.22319] [PMID: 31335990]
[77]
Bradley-Whitman, M.A.; Lovell, M.A. Epigenetic changes in the progression of Alzheimer’s disease. Mech. Ageing Dev., 2013, 134(10), 486-495.
[http://dx.doi.org/10.1016/j.mad.2013.08.005] [PMID: 24012631]
[78]
Blanch, M.; Mosquera, J.L.; Ansoleaga, B.; Ferrer, I.; Barrachina, M. Altered mitochondrial DNA methylation pattern in Alzheimer disease-related pathology and in Parkinson disease. Am. J. Pathol., 2016, 186(2), 385-397.
[http://dx.doi.org/10.1016/j.ajpath.2015.10.004] [PMID: 26776077]
[79]
Stoccoro, A.; Siciliano, G.; Migliore, L.; Coppedè, F. Decreased methylation of the mitochondrial D-loop region in late-onset Alzheimer’s disease. J. Alzheimers Dis., 2017, 59(2), 559-564.
[http://dx.doi.org/10.3233/JAD-170139] [PMID: 28655136]
[80]
Chestnut, B.A.; Chang, Q.; Price, A.; Lesuisse, C.; Wong, M.; Martin, L.J. Epigenetic regulation of motor neuron cell death through DNA methylation. J. Neurosci., 2011, 31(46), 16619-16636.
[http://dx.doi.org/10.1523/JNEUROSCI.1639-11.2011] [PMID: 22090490]
[81]
Jęśko, H.; Wencel, P.; Strosznajder, R.P.; Strosznajder, J.B. Sirtuins and their roles in brain aging and neurodegenerative disorders. Neurochem. Res., 2017, 42(3), 876-890.
[http://dx.doi.org/10.1007/s11064-016-2110-y] [PMID: 27882448]
[82]
Cieślik, M.; Czapski, G.A.; Strosznajder, J.B. The molecular mechanism of amyloid β42 peptide toxicity: The role of sphingosine kinase-1 and mitochondrial sirtuins. PLoS One, 2015, 10(9), e0137193.
[http://dx.doi.org/10.1371/journal.pone.0137193] [PMID: 26334640]
[83]
Yang, W.; Zou, Y.; Zhang, M.; Zhao, N.; Tian, Q.; Gu, M.; Liu, W.; Shi, R.; Lü, Y.; Yu, W. Mitochondrial Sirt3 expression is decreased in APP/PS1 double transgenic mouse model of Alzheimer’s disease. Neurochem. Res., 2015, 40(8), 1576-1582.
[http://dx.doi.org/10.1007/s11064-015-1630-1] [PMID: 26045440]
[84]
Guan, Q.; Wang, M.; Chen, H.; Yang, L.; Yan, Z.; Wang, X. Aging-related 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurochemial and behavioral deficits and redox dysfunction: Improvement by AK-7. Exp. Gerontol., 2016, 82, 19-29.
[http://dx.doi.org/10.1016/j.exger.2016.05.011] [PMID: 27235848]
[85]
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Mathew, G.E.; Uddin, M.S.; Kim, H.; Mathew, B. Advancements in nanotherapeutics for Alzheimer’s disease: Current perspectives. J. Pharm. Pharmacol., 2019, 71(9), 1370-1383.
[http://dx.doi.org/10.1111/jphp.13132] [PMID: 31304982]
[86]
Narayanan, S.E.; Rehuman, N.A.; Harilal, S.; Vincent, A.; Rajamma, R.G.; Behl, T.; Uddin, M.S.; Ashraf, G.M.; Mathew, B. Molecular mechanism of zinc neurotoxicity in Alzheimer’s disease. Environ. Sci. Pollut. Res. Int., 2020, 27(35), 43542-43552.
[http://dx.doi.org/10.1007/s11356-020-10477-w] [PMID: 32909132]
[87]
Harilal, S.; Jose, J.; Parambi, D.G.T.; Kumar, R.; Unnikrishnan, M.K.; Uddin, M.S.; Mathew, G.E.; Pratap, R.; Marathakam, A.; Mathew, B. Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules. Brain Res. Bull., 2020, 160, 121-140.
[http://dx.doi.org/10.1016/j.brainresbull.2020.03.018] [PMID: 32315731]
[88]
Alexiou, A.; Nizami, B.; Khan, F.I.; Soursou, G.; Vairaktarakis, C.; Chatzichronis, S.; Tsiamis, V.; Manztavinos, V.; Yarla, N.S.; Md Ashraf, G. Mitochondrial dynamics and proteins related to neurodegenerative diseases. Curr. Protein Pept. Sci., 2018, 19(9), 850-857.
[http://dx.doi.org/10.2174/1389203718666170810150151] [PMID: 28799502]
[89]
Cottrell, D.A.; Blakely, E.L.; Johnson, M.A.; Ince, P.G.; Turnbull, D.M. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology, 2001, 57(2), 260-264.
[http://dx.doi.org/10.1212/WNL.57.2.260] [PMID: 11468310]
[90]
Kish, S.J.; Bergeron, C.; Rajput, A.; Dozic, S.; Mastrogiacomo, F.; Chang, L-J.; Wilson, J.M.; DiStefano, L.M.; Nobrega, J.N. Brain cytochrome oxidase in Alzheimer’s disease. J. Neurochem., 1992, 59(2), 776-779.
[http://dx.doi.org/10.1111/j.1471-4159.1992.tb09439.x] [PMID: 1321237]
[91]
de Leon, M.J.; Ferris, S.H.; George, A.E.; Christman, D.R.; Fowler, J.S.; Gentes, C.; Reisberg, B.; Gee, B.; Emmerich, M.; Yonekura, Y.; Brodie, J.; Kricheff, I.I.; Wolf, A.P. Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am. J. Neuroradiol., 1983, 4(3), 568-571.
[PMID: 6410799]
[92]
Small, G.W.; Ercoli, L.M.; Silverman, D.H.; Huang, S-C.; Komo, S.; Bookheimer, S.Y.; Lavretsky, H.; Miller, K.; Siddarth, P.; Rasgon, N.L.; Mazziotta, J.C.; Saxena, S.; Wu, H.M.; Mega, M.S.; Cummings, J.L.; Saunders, A.M.; Pericak-Vance, M.A.; Roses, A.D.; Barrio, J.R.; Phelps, M.E. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2000, 97(11), 6037-6042.
[http://dx.doi.org/10.1073/pnas.090106797] [PMID: 10811879]
[93]
Lustbader, J.W.; Cirilli, M.; Lin, C.; Xu, H.W.; Takuma, K.; Wang, N.; Caspersen, C.; Chen, X.; Pollak, S.; Chaney, M.; Trinchese, F.; Liu, S.; Gunn-Moore, F.; Lue, L.F.; Walker, D.G.; Kuppusamy, P.; Zewier, Z.L.; Arancio, O.; Stern, D.; Yan, S.S.; Wu, H. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science, 2004, 304(5669), 448-452.
[http://dx.doi.org/10.1126/science.1091230] [PMID: 15087549]
[94]
Parker, W.D., Jr; Parks, J.; Filley, C.M.; Kleinschmidt-DeMasters, B.K. Electron transport chain defects in Alzheimer’s disease brain. Neurology, 1994, 44(6), 1090-1096.
[http://dx.doi.org/10.1212/WNL.44.6.1090] [PMID: 8208407]
[95]
Parker, W.D., Jr; Filley, C.M.; Parks, J.K. Cytochrome oxidase deficiency in Alzheimer’s disease. Neurology, 1990, 40(8), 1302-1303.
[http://dx.doi.org/10.1212/WNL.40.8.1302] [PMID: 2166249]
[96]
Alexiou, A.; Soursou, G.; Chatzichronis, S.; Gasparatos, E.; Kamal, M.A.; Yarla, N.S.; Perveen, A.; Barreto, G.E.; Ashraf, G.M. Role of GTPases in the regulation of mitochondrial dynamics in Alzheimer’s disease and CNS-related disorders. Mol. Neurobiol., 2019, 56(6), 4530-4538.
[http://dx.doi.org/10.1007/s12035-018-1397-x] [PMID: 30338485]
[97]
Alexiou, A.; Chatzichronis, S.; Ashraf, G.M. Prediction of Alzheimer’s disease. Diagnosis and Management in Dementia; Elsevier, 2020, pp. 365-378.
[http://dx.doi.org/10.1016/B978-0-12-815854-8.00023-9]
[98]
Hudson, G.; Sims, R.; Harold, D.; Chapman, J.; Hollingworth, P.; Gerrish, A.; Russo, G.; Hamshere, M.; Moskvina, V.; Jones, N.; Thomas, C.; Stretton, A.; Holmans, P.A.; O’Donovan, M.C.; Owen, M.J.; Williams, J.; Chinnery, P.F. No consistent evidence for association between mtDNA variants and Alzheimer disease. Neurology, 2012, 78(14), 1038-1042.
[http://dx.doi.org/10.1212/WNL.0b013e31824e8f1d] [PMID: 22442439]
[99]
Edland, S.D.; Silverman, J.M.; Peskind, E.R.; Tsuang, D.; Wijsman, E.; Morris, J.C. Increased risk of dementia in mothers of Alzheimer’s disease cases: Evidence for maternal inheritance. Neurology, 1996, 47(1), 254-256.
[http://dx.doi.org/10.1212/WNL.47.1.254] [PMID: 8710088]
[100]
Coskun, P.E.; Beal, M.F.; Wallace, D.C. Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc. Natl. Acad. Sci. USA, 2004, 101(29), 10726-10731.
[http://dx.doi.org/10.1073/pnas.0403649101] [PMID: 15247418]
[101]
Chinnery, P.F.; Taylor, G.A.; Howell, N.; Brown, D.T.; Parsons, T.J.; Turnbull, D.M. Point mutations of the mtDNA control region in normal and neurodegenerative human brains. Am. J. Hum. Genet., 2001, 68(2), 529-532.
[http://dx.doi.org/10.1086/318204] [PMID: 11133363]
[102]
Howell, N.; Elson, J.L.; Chinnery, P.F.; Turnbull, D.M. mtDNA mutations and common neurodegenerative disorders. Trends Genet., 2005, 21(11), 583-586.
[http://dx.doi.org/10.1016/j.tig.2005.08.012] [PMID: 16154228]
[103]
Lin, M.T.; Simon, D.K.; Ahn, C.H.; Kim, L.M.; Beal, M.F. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer’s disease brain. Hum. Mol. Genet., 2002, 11(2), 133-145.
[http://dx.doi.org/10.1093/hmg/11.2.133] [PMID: 11809722]
[104]
Parambi, D.G.T.; Saleem, U.; Shah, M.A.; Anwar, F.; Ahmad, B.; Manzar, A.; Itzaz, A.; Harilal, S.; Uddin, M.S.; Kim, H.; Mathew, B. Exploring the therapeutic potentials of highly selective oxygenated chalcone based MAO-B inhibitors in a haloperidol-induced murine model of Parkinson’s disease. Neurochem. Res., 2020, 45(11), 2786-2799.
[http://dx.doi.org/10.1007/s11064-020-03130-y] [PMID: 32939670]
[105]
Palakkathondi, A.; Oh, J.M.; Dev, S.; Rangarajan, T.M.; Kaipakasseri, S.; Kavully, F.S.; Gambacorta, N.; Nicolotti, O.; Kim, H.; Mathew, B. (Hetero-)(arylidene)arylhydrazides as Multitarget-Directed Monoamine Oxidase Inhibitors. ACS Comb. Sci., 2020, 22(11), 592-599.
[http://dx.doi.org/10.1021/acscombsci.0c00136] [PMID: 33047950]
[106]
Chaudhary, S.S.; Chaudhary, S.; Rawat, S.; Natesan, S.; Pardeshi, T.; Alexiou, A. Recent developments in the etiology, treatment, and potential therapeutic targets for Parkinson’s disease: A focus on biochemistry.Diagnosis and Management in Parkinson’s Disease; Elsevier, 2020, pp. 73-90.
[http://dx.doi.org/10.1016/B978-0-12-815946-0.00005-3]
[107]
Mapa, M.S.T.; Le, V.Q.; Wimalasena, K. Characteristics of the mitochondrial and cellular uptake of MPP+, as probed by the fluorescent mimic, 4'I-MPP. PLoS One, 2018, 13(8), e0197946.
[http://dx.doi.org/10.1371/journal.pone.0197946] [PMID: 30138351]
[108]
Subramaniam, S.R.; Chesselet, M-F. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog. Neurobiol., 2013, 106-107, 17-32.
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.004] [PMID: 23643800]
[109]
Itoh, K.; Weis, S.; Mehraein, P.; Müller-Höcker, J. Cytochrome c oxidase defects of the human substantia nigra in normal aging. Neurobiol. Aging, 1996, 17(6), 843-848.
[http://dx.doi.org/10.1016/S0197-4580(96)00168-6] [PMID: 9363794]
[110]
Perier, C.; Bender, A.; García-Arumí, E.; Melià, M.J.; Bové, J.; Laub, C.; Klopstock, T.; Elstner, M.; Mounsey, R.B.; Teismann, P.; Prolla, T.; Andreu, A.L.; Vila, M. Accumulation of mitochondrial DNA deletions within dopaminergic neurons triggers neuroprotective mechanisms. Brain, 2013, 136(Pt 8), 2369-2378.
[http://dx.doi.org/10.1093/brain/awt196] [PMID: 23884809]
[111]
Reeve, A.K.; Park, T-K.; Jaros, E.; Campbell, G.R.; Lax, N.Z.; Hepplewhite, P.D.; Krishnan, K.J.; Elson, J.L.; Morris, C.M.; McKeith, I.G.; Turnbull, D.M. Relationship between mitochondria and α-synuclein: A study of single Substantia nigra neurons. Arch. Neurol., 2012, 69(3), 385-393.
[http://dx.doi.org/10.1001/archneurol.2011.2675] [PMID: 22410447]
[112]
Müller, S.K.; Bender, A.; Laub, C.; Högen, T.; Schlaudraff, F.; Liss, B.; Klopstock, T.; Elstner, M. Lewy body pathology is associated with mitochondrial DNA damage in Parkinson’s disease. Neurobiol. Aging, 2013, 34(9), 2231-2233.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.03.016] [PMID: 23566333]
[113]
Lin, M.T.; Beal, M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113), 787-795.
[http://dx.doi.org/10.1038/nature05292] [PMID: 17051205]
[114]
Beal, M.F. Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol., 2005, 58(4), 495-505.
[http://dx.doi.org/10.1002/ana.20624] [PMID: 16178023]
[115]
Grazina, M.; Silva, F.; Santana, I.; Santiago, B.; Mendes, C.; Simões, M.; Oliveira, M.; Cunha, L.; Oliveira, C. Frontotemporal dementia and mitochondrial DNA transitions. Neurobiol. Dis., 2004, 15(2), 306-311.
[http://dx.doi.org/10.1016/j.nbd.2003.11.004] [PMID: 15006700]
[116]
Rosen, D.R.; Siddique, T.; Patterson, D.; Figlewicz, D.A.; Sapp, P.; Hentati, A.; Donaldson, D.; Goto, J.; O’Regan, J.P.; Deng, H.X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 1993, 362(6415), 59-62.
[http://dx.doi.org/10.1038/362059a0] [PMID: 8446170]
[117]
Comi, G.P.; Bordoni, A.; Salani, S.; Franceschina, L.; Sciacco, M.; Prelle, A.; Fortunato, F.; Zeviani, M.; Napoli, L.; Bresolin, N.; Moggio, M.; Ausenda, C.D.; Taanman, J.W.; Scarlato, G. Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann. Neurol., 1998, 43(1), 110-116.
[http://dx.doi.org/10.1002/ana.410430119] [PMID: 9450776]
[118]
Zoccolella, S.; Artuso, L.; Capozzo, R.; Amati, A.; Guerra, F.; Simone, I.; Logroscino, G.; Petruzzella, V. Mitochondrial genome large rearrangements in the skeletal muscle of a patient with PMA. Eur. J. Neurol., 2012, 19(7), e63-e64.
[http://dx.doi.org/10.1111/j.1468-1331.2012.03720.x] [PMID: 22691093]
[119]
Polito, L.; Biella, G.; Albani, D. Sirtuin modulation as novel neuroprotective strategy for Alzheimer’s disease.Neuroprotection in Alzheimer’s Disease; Elsevier, 2017, pp. 149-173.
[http://dx.doi.org/10.1016/B978-0-12-803690-7.00008-9]
[120]
Hwang, E.S. Pharmacological nicotinamide: mechanisms centered around SIRT1 activity. Pharmacoepigenetics; Elsevier, 2019, pp. 781-799.
[http://dx.doi.org/10.1016/B978-0-12-813939-4.00029-2]
[121]
Corona, J.C.; Duchen, M.R. PPARγ and PGC-1α as therapeutic targets in Parkinson’s. Neurochem. Res., 2015, 40(2), 308-316.
[http://dx.doi.org/10.1007/s11064-014-1377-0] [PMID: 25007880]
[122]
Müller, T.; Büttner, T.; Gholipour, A-F.; Kuhn, W. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson’s disease. Neurosci. Lett., 2003, 341(3), 201-204.
[http://dx.doi.org/10.1016/S0304-3940(03)00185-X] [PMID: 12697283]
[123]
Kieburtz, K.; Ravina, B.; Galpern, W.R.; Tilley, B.; Shannon, K.; Tanner, C. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology, 2007, 68(1), 20-28.
[http://dx.doi.org/10.1212/01.wnl.0000250355.28474.8e] [PMID: 17200487]

Rights & Permissions Print Cite
Article Metrics
40
1
World Autism Awareness Day
© 2024 Bentham Science Publishers | Privacy Policy