title: Molecular pathways in sporadic PD.
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.
authors.affiliation: Neurogenetics Unit, CSS-Mendel Institute, Rome, Italy.
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arena
authors.forename: Liliana
authors.initials: L
authors.lastname: Torosantucci
authors.forename: Vania
authors.initials: V
authors.lastname: Gelmetti
mesh_terms: D000818:Animals; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D009434:Neural Pathways / Q000201:enzymology / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics
chemical_list: D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases