The role of α-Synuclein in neurodegenerative diseases: From molecular pathways in disease to therapeutic approaches

Karima M. Al-Mansoori, Mohamed Y. Hasan, Abdulmonem Al-Hayani, Omar M.A. El-Agnaf

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)559-568
Number of pages10
JournalCurrent Alzheimer Research
Volume10
Issue number6
DOIs
Publication statusPublished - 28 Aug 2013

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Keywords

  • Alpha-synuclein
  • Alzheimer's disease
  • Dementia with lewy bodies and protein aggregation
  • Drug discovery
  • Lewy bodies
  • Neurodegeneration
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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