A mitochondrial etiology of neurodegenerative diseases: evidence from Parkinson's disease

Ann N Y Acad Sci. 2008 Dec;1147:1-20. doi: 10.1196/annals.1427.001.

Abstract

Evidence continues to accrue implicating mitochondrial dysfunction in the etiology of a number of neurodegenerative diseases. For example, Parkinson's disease (PD) can be induced by mitochondrial toxins, and nuclear DNA (nDNA) loci linked to PD have been associated with mitochondrial dysfunction. Although conclusions about the role of mitochondrial DNA (mtDNA) variants in PD vary, we argue here that this is attributable to the novel genetics of the mtDNA and the fact that clinically relevant mtDNA variation encompasses ancient adaptive polymorphisms, recent deleterious mutations, and somatic mutations. An mtDNA association with PD is supported by an analysis of the Russian Tatar population which revealed that polymorphisms associated with haplogroup H mtDNAs increased PD risk (odds ratio [OR]= 2.58, P= 0.0001), whereas those associated with haplogroup UK cluster mtDNAs were protective (OR = 0.38, P= 0.003). Moreover, mtDNA sequencing revealed that PD patients with either haplogroup H or UK cluster mtDNAs can harbor additional recent variants that might further modulate PD risk. Therefore, the complexity of PD genetics may reflect the complex mitochondrial genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Case-Control Studies
  • DNA Primers
  • DNA, Mitochondrial / genetics
  • Haplotypes
  • Humans
  • Middle Aged
  • Mitochondria / physiology*
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics
  • Parkinson Disease / physiopathology

Substances

  • DNA Primers
  • DNA, Mitochondrial