BethAnn McLaughlin
Faculty Member
Last active: 4/25/2016

The role of central nervous system development in late-onset neurodegenerative disorders.

Palubinsky AM, Martin JA, McLaughlin B
Dev Neurosci. 2012 34 (2-3): 129-39

PMID: 22572535 · PMCID: PMC6065248 · DOI:10.1159/000336828

The human brain is dependent upon successfully maintaining ionic, energetic and redox homeostasis within exceptionally narrow margins for proper function. The ability of neurons to adapt to genetic and environmental perturbations and evoke a 'new normal' can be most fully appreciated in the context of neurological disorders in which clinical impairments do not manifest until late in life, although dysfunctional proteins are expressed early in development. We now know that proteins controlling ATP generation, mitochondrial stability, and the redox environment are associated with neurological disorders such as Parkinson's disease and amyotrophic lateral sclerosis. Generally, focus is placed on the role that early or long-term environmental stress has in altering the survival of cells targeted by genetic dysfunctions; however, the central nervous system undergoes several periods of intense stress during normal maturation. One of the most profound periods of stress occurs when 50% of neurons are removed via programmed cell death. Unfortunately, we have virtually no understanding of how these events proceed in individuals who harbor mutations that are lethal later in life. Moreover, there is a profound lack of information on circuit formation, cell fate during development and neurochemical compensation in either humans or the animals used to model neurodegenerative diseases. In this review, we consider the current knowledge of how energetic and oxidative stress signaling differs between neurons in early versus late stages of life, the influence of a new group of proteins that can integrate cell stress signals at the mitochondrial level, and the growing body of evidence that suggests early development should be considered a critical period for the genesis of chronic neurodegenerative diseases.

Copyright © 2012 S. Karger AG, Basel.

MeSH Terms (8)

Brain Cell Death Humans Nerve Degeneration Neurodegenerative Diseases Neurons Oxidative Stress Reactive Oxygen Species

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