Title:The Role of α-Synuclein in Neurodegenerative Diseases: From Molecular Pathways in Disease to Therapeutic Approaches
VOLUME: 10 ISSUE: 6
Author(s):Karima M. Al-Mansoori, Mohamed Y. Hasan, Abdulmonem Al-Hayani and Omar M.A. El-Agnaf
Affiliation:Department of Biochemistry, Faculty of Medicine and Health Science, UAE University, PO Box 17666, Al- Ain, UAE.
Keywords:Alpha-synuclein, alzheimer’ s disease, drug discovery, lewy bodies, neurodegeneration, parkinson’ s disease, dementia
with lewy bodies and protein aggregation.
Abstract:Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer’s disease
(AD). The formation of the cytoplasmic inclusions named “Lewy bodies” in the brain, considered to be a marker for neuronal
degeneration in PD and dementia with Lewy bodies. However, Lewy bodies (LBs) are also observed in approximately
60 percent of both sporadic and familial cases with AD. LBs consist of fibrils mainly formed by post-translational
modified α-synuclein (α-syn) protein. The modifications can be truncation, phosphorylation, nitration and mono-, di-, or
tri-ubiquitination. Development of disease seems to be linked to events that increase the concentration of α-syn or cause
its chemical modification, either of which can accelerate α-syn aggregation. Examples of such events include increased
copy number of genes, decreased rate of degradation via the proteasome or other proteases, or modified forms of α-syn.
As the aggregation of α-syn in the brain has been strongly implicated as a critical step in the development of several neurodegenerative
diseases, the current search for disease-modifying drugs is focused on modification of the process of α-syn
deposition in the brain. Recently researchers have screened and designed various molecules that are selectively focused on
inhibiting or preventing α-syn aggregation and toxicity. Another strategy that has emerged is to target α-syn expression as
a potential therapy for neurodegenerative diseases associated with LBs.
