title: Candidate genes for Parkinson disease: Lessons from pathogenesis.
abstract: Parkinson disease (PD) is a multifactorial neurodegenerative disease characterized by the progressive loss of specific neuronal populations and accumulation of Lewy bodies in the brain, leading to motor and non-motor symptoms. In a small subset of patients, PD is dominantly or recessively inherited, while a number of susceptibility genetic loci have been identified through genome wide association studies. The discovery of genes mutated in PD and functional studies on their protein products have provided new insights into the molecular events leading to neurodegeneration, suggesting that few interconnected molecular pathways may be deranged in all forms of PD, triggering neuronal loss. Here, we summarize the most relevant findings implicating the main PD-related proteins in biological processes such as mitochondrial dysfunction, misfolded protein damage, alteration of cellular clearance systems, abnormal calcium handling and altered inflammatory response, which represent key targets for neuroprotection.
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, San Giovanni Rotondo, Italy.
authors.forename: Priscilla
authors.initials: P
authors.lastname: De Rosa
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, San Giovanni Rotondo, Italy; Dept. of Biological and Environmental Sciences, University of Messina, Messina, Italy.
authors.forename: Elettra Sara
authors.initials: ES
authors.lastname: Marini
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, San Giovanni Rotondo, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Gelmetti
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, San Giovanni Rotondo, Italy; Section of Neurosciences, Dept. of Medicine and Surgery, University of Salerno, Salerno, Italy. Electronic address: e.valente@css-mendel.it.
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D001343:Autophagy / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*
keywords: Autophagy; Genetics; Inflammation; Misfolded protein damage; Mitochondria; Parkinson disease