title: Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness.
abstract: The selective cell loss in the ventral component of the substantia nigra pars compacta and the presence of alpha-synuclein (α-syn)-rich intraneuronal inclusions called Lewy bodies are the pathological hallmarks of Parkinson's disease (PD), the most common motor system disorder whose aetiology remains largely elusive. Although most cases of PD are idiopathic, there are rare familial forms of the disease that can be traced to single gene mutations that follow Mendelian inheritance pattern. The study of several nuclear encoded proteins whose mutations are linked to the development of autosomal recessive and dominant forms of familial PD enhanced our understanding of biochemical and cellular mechanisms contributing to the disease and suggested that many signs of neurodegeneration result from compromised mitochondrial function. Here we present an overview of the current understanding of PD-related mitochondrial dysfunction including defects in bioenergetics and Ca2+homeostasis, mitochondrial DNA mutations, altered mitochondrial dynamics and autophagy. We emphasize, in particular, the convergence of many "apparently" different pathways towards a common route involving mitochondria. Understanding whether mitochondrial dysfunction in PD represents the cause or the consequence of the disease is challenging and will help to define the pathogenic processes at the basis of the PD onset and progression.
authors: Dept. of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
authors: Domenico
authors: D
authors: Cieri
authors: Dept. of Biology, University of Padova, 35131 Padova, Italy.
authors: Marisa
authors: M
authors: Brini
authors: Dept. of Biomedical Sciences, University of Padova, 35131 Padova, Italy. Electronic address: tito.cali@unipd.it.
authors: Tito
authors: T
authors: Calì
mesh_terms: D000818:Animals; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D002118:Calcium
keywords: Calcium; Dopaminergic neurons; Mitochondria; PD-related proteins; Parkinson disease