Molecular pathways in sporadic PD

Enza Maria Valente, Giuseppe Arena, Liliana Torosantucci, Vania Gelmetti

Research output: Contribution to journalArticle

Abstract

Over the last decade, several autosomal dominant and recessive genes causative of Parkinson's disease (PD) have been identified. The functional studies on their protein products and the pathogenetic effect related to their mutations have greatly contributed to understand the many cellular pathways leading to neurodegeneration, that include oxidative stress damage, mitochondrial dysfunction, misfolded protein stress and impairment of cellular clearance systems, namely the ubiquitin-proteasome system (UPS) and the autophagy pathway. Although mendelian genes are responsible only for a small subset of PD patients, it is expected that the same pathogenetic mechanisms could play a relevant role also in the more frequent sporadic PD, that is currently recognized as a multifactorial disorder. In this model, different genetic and environmental factors, either playing a protective or a susceptibility role, variably interact to reach a threshold of disease over which PD will become clinically manifest. As an example, mutations or multiplication of the alpha-synuclein gene cause autosomal dominant PD, while common genetic variants at the same locus have been consistently associated to the risk of developing PD by genome-wide association studies. These findings are opening novel interesting perspectives to identify critical molecular pathways leading to neurodegeneration.

Original languageEnglish
JournalParkinsonism and Related Disorders
Volume18
Issue numberSUPPL. 1
Publication statusPublished - Jan 2012

    Fingerprint

Keywords

  • Alpha-synuclein
  • Autophagy
  • Genetics
  • Mitochondria
  • Molecular pathways
  • Protein aggregates
  • Sporadic Parkinson's disease

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

Cite this

Valente, E. M., Arena, G., Torosantucci, L., & Gelmetti, V. (2012). Molecular pathways in sporadic PD. Parkinsonism and Related Disorders, 18(SUPPL. 1).