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Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease
Author(s) -
Calì Tito,
Ottolini Denis,
Brini Marisa
Publication year - 2011
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.159
Subject(s) - substantia nigra , pars compacta , neurodegeneration , endoplasmic reticulum , proteasome , dopaminergic , parkinson's disease , biology , unfolded protein response , mitochondrion , microbiology and biotechnology , oxidative stress , alpha synuclein , neuroscience , disease , pathology , medicine , dopamine , endocrinology
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNPC) and the presence of intracytoplasmatic inclusions known as Lewy bodies, largely composed of alpha‐synuclein (α‐syn). PD is a multifactorial disease and its etiology remains largely elusive. Although more than 90% of the cases are sporadic, mutations in several nuclear encoded genes have been linked to the development of autosomal recessive and dominant familial parkinsonian syndromes (Bogaerts et al. (2008) Genes Brain Behav 7, 129–151), enhancing our understanding of biochemical and cellular mechanisms contributing to the disease. Many cellular mechanisms are thought to be involved in the dopaminergic neuronal death in PD, including oxidative stress, intracellular Ca 2+ homeostasis impairment, and mitochondrial dysfunctions. Furthermore, endoplasmic reticulum (ER) stress together with abnormal protein degradation by the ubiquitin proteasome system is considered to contribute to the PD pathogenesis. This review covers all the aspects related to the molecular mechanisms underlying the interplay between mitochondria, ER, and proteasome system in PD‐associated neurodegeneration.