Neurodegenerative disorders and ischemic brain diseases

M. P. Mattson, W. Duan, W. A. Pedersen, C. Culmsee

Research output: Contribution to journalReview article

Abstract

Degeneration and death of neurons is the fundamental process responsible for the clinical manifestations of many different neurological disorders of aging, including Alzheimer's disease, Parkinson's disease and stroke. The death of neurons in such disorders involves apoptotic biochemical cascades involving upstream effectors (Par-4, p53 and pro-apoptotic Bcl-2 family members), mitochondrial alterations and caspase activation. Both genetic and environmental factors, and the aging process itself, contribute to initiation of such neuronal apoptosis. For example, mutations in the amyloid precursor protein and presenilin genes can cause Alzheimer's disease, while head injury is a risk factor for both Alzheimer's and Parkinson's diseases. At the cellular level, neuronal apoptosis in neurodegenerative disorders may be triggered by oxidative stress, metabolic compromise and disruption of calcium homeostasis. Neuroprotective (anti-apoptotic) signaling pathways involving neurotrophic factors, cytokines and "conditioning responses" can counteract the effects of aging and genetic predisposition in experimental models of neurodegenerative disorders. A better understanding of the molecular underpinnings of neuronal death is leading directly to novel preventative and therapeutic approaches to neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)69-81
Number of pages13
JournalApoptosis
Volume6
Issue number1-2
DOIs
StatePublished - Apr 3 2001
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Caspases
  • Mitochondrial permeability transition
  • Neurotrophic factors
  • Oxidative stress
  • Parkinson's disease
  • Telomerase

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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