Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders

Guangyu Gu, Patricio F. Reyes, Gregory T. Golden, Randall (Randy) Woltjer, Christine Hulette, Thomas J. Montine, Jing Zhang

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Inhibition of mitochondrial respiratory chain function may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson disease (PD). Since large-scale structural changes (e.g. deletions and rearrangements in mitochondrial DNA [mtDNA]) have been associated with mitochondrial dysfunction, we tested the hypothesis that increased total mtDNA deletions/rearrangements are associated with neurodegeneration in PD. This study employed a well-established technique, long-extension polymerase chain reaction (LX-PCR), to detect the multiple mtDNA deletions/ rearrangements in the SN of patients with PD, multiple system atrophy (MSA), dementia with Lewy bodies (DLB), Alzheimer disease (AD), and age-matched controls. We also compared the total mtDNA deletions/rearrangements in different brain regions of PD patients. The results demonstrated that both the number and variety of mtDNA deletions/rearrangements were selectively increased in the SN of PD patients compared to patients with other movement disorders as well as patients with AD and age-matched controls. In addition, increased mtDNA deletions/rearrangements were observed in other brain regions in PD patients, indicating that mitochondrial dysfunction is not just limited to the SN of PD patients. These data suggest that accumulation of total mtDNA deletions/rearrangements is a relatively specific characteristic of PD and may be one of the contributing factors leading to mitochondrial dysfunction and neurodegeneration in PD.

Original languageEnglish (US)
Pages (from-to)634-639
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume61
Issue number7
StatePublished - 2002
Externally publishedYes

Fingerprint

Gene Rearrangement
Mitochondrial DNA
Neurodegenerative Diseases
Parkinson Disease
Substantia Nigra
Alzheimer Disease
Multiple System Atrophy
Lewy Body Disease
Movement Disorders
Brain
Electron Transport
Dementia
Polymerase Chain Reaction

Keywords

  • Aging
  • Energy metabolism
  • Free radicals
  • Mitochondria
  • Oxidative stress
  • Parkinsonism

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders. / Gu, Guangyu; Reyes, Patricio F.; Golden, Gregory T.; Woltjer, Randall (Randy); Hulette, Christine; Montine, Thomas J.; Zhang, Jing.

In: Journal of Neuropathology and Experimental Neurology, Vol. 61, No. 7, 2002, p. 634-639.

Research output: Contribution to journalArticle

Gu, Guangyu ; Reyes, Patricio F. ; Golden, Gregory T. ; Woltjer, Randall (Randy) ; Hulette, Christine ; Montine, Thomas J. ; Zhang, Jing. / Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders. In: Journal of Neuropathology and Experimental Neurology. 2002 ; Vol. 61, No. 7. pp. 634-639.
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