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Current Genomics
ISSN (Print): 1389-2029
ISSN (Online): 1875-5488
VOLUME: 14
ISSUE: 8
DOI: 10.2174/1389202914666131210205839









Mutations in PRKN and SNCA Genes Important for the Progress of Parkinson’s Disease

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Author(s): Anna Oczkowska, Wojciech Kozubski, Margarita Lianeri and Jolanta Dorszewska
Pages 502-517 (16)
Abstract:
Although Parkinson’s disease (PD) was first described almost 200 years ago, it remains an incurable disease with a cause that is not fully understood. Nowadays it is known that disturbances in the structure of pathological proteins in PD can be caused by more than environmental and genetic factors. Despite numerous debates and controversies in the literature about the role of mutations in the SNCA and PRKN genes in the pathogenesis of PD, it is evident that these genes play a key role in maintaining dopamine (DA) neuronal homeostasis and that the dysfunction of this homeostasis is relevant to both familial (FPD) and sporadic (SPD) PD with different onset. In recent years, the importance of alphasynuclein (ASN) in the process of neurodegeneration and neuroprotective function of the Parkin is becoming better understood. Moreover, there have been an increasing number of recent reports indicating the importance of the interaction between these proteins and their encoding genes. Among others interactions, it is suggested that even heterozygous substitution in the PRKN gene in the presence of the variants +2/+2 or +2/+3 of NACP-Rep1 in the SNCA promoter, may increase the risk of PD manifestation, which is probably due to ineffective elimination of over-expressed ASN by the mutated Parkin protein. Finally, it seems that genetic testing may be an important part of diagnostics in patients with PD and may improve the prognostic process in the course of PD. However, only full knowledge of the mechanism of the interaction between the genes associated with the pathogenesis of PD is likely to help explain the currently unknown pathways of selective damage to dopaminergic neurons in the course of PD.
Keywords:
Alpha-synuclein, Parkin, Parkinson’s disease, PRKN, SNCA.
Affiliation:
Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49 Przybyszewskiego St, 60-355 Poznan, Poland.