Mitochondria, calcium, and endoplasmic reticulum stress in Parkinson's disease

Authors

  • Tito Calì,

    1. Department of Biological Chemistry, University of Padova, Padova, Italy
    2. Department of Experimental Veterinary Sciences, University of Padova, Padova, Italy
    Search for more papers by this author
  • Denis Ottolini,

    1. Department of Biological Chemistry, University of Padova, Padova, Italy
    2. Department of Experimental Veterinary Sciences, University of Padova, Padova, Italy
    Search for more papers by this author
  • Marisa Brini

    Corresponding author
    1. Department of Biological Chemistry, University of Padova, Padova, Italy
    • PhD, Department of Biological Chemistry, University of Padova, Viale G. Colombo, 3, 35131 Padova, Italy
    Search for more papers by this author
    • Tel.: +39-049-827-6150; Fax: +39-049-827-6125


Abstract

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 Ca2+ 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.

Ancillary