Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders

Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


When subjected to excessive oxidative stress, neurons may respond adaptively to overcome the stress, or they may activate a programmed cell death pathway called apoptosis. Apoptosis is characterized by alterations in mitochondria and the endoplasmic reticulum and activation of cysteine proteases called caspases. Increasing evidence suggests that apoptotic biochemical cascades are involved in the dysfunction and death of neurons in neurodegenerative disorders such as Alzheimer's, Parkinson, and Huntington's diseases. Studies of normal aging, of genetic mutations that cause disease, and of environmental factors that affect disease risk are revealing cellular and molecular alterations that may cause excessive oxidative stress and trigger neuronal apoptosis. Accumulation of self-aggregating proteins such as amyloid β-peptide, tau, α-synuclein, and huntingtin may be involved in apoptosis both upstream and downstream of oxidative stress. Membrane-associated oxidative stress resulting in perturbed lipid metabolism and disruption of cellular calcium homeostasis may trigger apoptosis in several different neurodegenerative disorders. Counteracting neurodegenerative processes are an array of mechanisms including neurotrophic factor signaling, antioxidant enzymes, protein chaperones, antiapoptotic proteins, and ionostatic systems. Emerging findings suggest that the resistance of neurons to death during aging can be enhanced by modifications of diet and lifestyle.

Original languageEnglish (US)
Pages (from-to)1997-2006
Number of pages10
JournalAntioxidants and Redox Signaling
Issue number11-12
StatePublished - Nov 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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