Pathogenesis of Parkinson's Disease

Amitabh Gupta, Ted M Dawson

Research output: Contribution to journalArticle

Abstract

This chapter focuses on the pathogenesis of Parkinson's disease (PD) and discusses more recent advances from neurogenetic research. Some observations from research that is not related to specific PD genes but appears to be converging with the insights obtained from neurogenetics are also highlighted. The molecular research data of proteins involved with pathogenesis of PD—namely, α-synuclein, parkin, leucine-rich repeat kinase-2 (LRRK2), DJ-1, and phosphatase and tensin homologue (PTEN)–induced putative kinase 1 (PINK1)—are presented. An important aspect of understanding PD pathogenesis involves the comprehension of the way in which α-synuclein is cleared from the cell. Intervening with α-synuclein accumulation presents a tremendous opportunity for developing an effective treatment. A molecular interaction between parkin and α-synuclein is an attractive unifying theory of PD pathogenesis. Because mutations in both proteins are also prominent genetic causes of familial PD, this would provide support for the notion that genetic interactions can indicate molecular interactions. Increased kinase activity of mutant LRRK2 and potentially abnormal or excessive phosphorylation of LRRK2 substrates directly trigger neurodegeneration and PD pathogenesis. It has become obvious over a short time that the PINK1-dependent signaling pathways are regulating the response of mitochondria to cell stress, emphasizing how mitochondrial dysfunction is central to PD pathogenesis. Cellular pacemaker activity and deacetylation are also discussed in the chapter.

Original languageEnglish (US)
Pages (from-to)155-169
Number of pages15
JournalBlue Books of Neurology
Volume34
Issue numberC
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Parkinson Disease
Synucleins
Phosphotransferases
Leucine
Research
Phosphoric Monoester Hydrolases
Mitochondria
Proteins
Phosphorylation
Mutation
Genes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Pathogenesis of Parkinson's Disease. / Gupta, Amitabh; Dawson, Ted M.

In: Blue Books of Neurology, Vol. 34, No. C, 01.01.2010, p. 155-169.

Research output: Contribution to journalArticle

Gupta, Amitabh ; Dawson, Ted M. / Pathogenesis of Parkinson's Disease. In: Blue Books of Neurology. 2010 ; Vol. 34, No. C. pp. 155-169.
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