Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat

@article{Mehler2000MechanismsUN,
  title={Mechanisms underlying neural cell death in neurodegenerative diseases: alterations of a developmentally-mediated cellular rheostat},
  author={Mark F. Mehler and Solen Gokhan},
  journal={Trends in Neurosciences},
  year={2000},
  volume={23},
  pages={599-605}
}
Genes associated with neurodegenerative diseases are normally expressed throughout neural development and are essential for the elaboration and maintenance of neuronal subpopulations. Disease-causing mutations can compromise defined subsets of these neural specification events in subtle ways that initially lead to impairments in the cellular homeostasis of evolving regional neuronal subpopulations, and adult-onset cell death from normally non-lethal environmental stressors. Neurodegenerative… 
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References

SHOWING 1-10 OF 64 REFERENCES
A one-hit model of cell death in inherited neuronal degenerations
TLDR
It is shown that the kinetics of neuronal death in 12 models of photoreceptor degeneration, hippocampal neurons undergoing excitotoxic cell death, a mouse model of cerebellar degeneration and Parkinson's and Huntington's diseases are all exponential and better explained by mathematical models in which the risk of cell death remains constant or decreases exponentially with age.
Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease
TLDR
It is demonstrated that a continuous influx of the mutant protein is required to maintain inclusions and symptoms of Huntington's disease, raising the possibility that HD may be reversible.
Molecular basis of the neurodegenerative disorders.
  • J. B. Martin
  • Medicine
    The New England journal of medicine
  • 1999
TLDR
Mendelian inheritance can be demonstrated in many of these disorders and senile plaques, neurofibrillary tangles, neuronal loss, and acetylcholine deficiency define Alzheimer's disease and Parkinson's disease.
The cell division cycle and the pathophysiology of Alzheimer's disease.
TLDR
The working hypothesis is that, contrary to previous belief, neurons in the adult human brain are capable of re-entering the cell division cycle and, in Alzheimer's disease the cell cycle is allowed to progress into the G2 phase.
Neuronal migration disorders: from genetic diseases to developmental mechanisms
TLDR
Many of the genes that control neuronal migration have strong genetic or biochemical links to the cytoskeleton, suggesting that the field of neuronal migration might be closing in on the underlying cytoskeletal events.
Presenilin-1 Mutation Increases Neuronal Vulnerability to Focal Ischemia In Vivo and to Hypoxia and Glucose Deprivation in Cell Culture: Involvement of Perturbed Calcium Homeostasis
TLDR
The data suggest that presenilin mutations may promote neuronal degeneration in AD by increasing the sensitivity of neurons to age-related ischemia-like conditions, and drugs that stabilize endoplasmic reticulum calcium homeostasis may prove effective in suppressing the neurodegenerative process in AD patients.
Linking DNA damage and neurodegeneration
TLDR
The current rapid progress in elucidation of molecular details following gene identification should provide further insight into the importance of DNA processing in nervous system function.
Skeletal and CNS Defects in Presenilin-1-Deficient Mice
TLDR
Results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival.
Disassembly of nuclear inclusions in the dividing cell--a novel insight into neurodegeneration.
TLDR
The studies indicate that the specific accumulation of inclusions in terminally differentiated cells such as neurons is a direct consequence of their inability to divide and therefore provides a key to explaining their persistence in neurodegenerative disease.
Expression of Presenilin 1 in nervous system during rat development
TLDR
It is proposed that presenilins participate in at least two different developmental processes: (1) one involved in neurogenesis and skeleton formation during embryonic development, probably involving coordinate expression with Notch, and (2) a second one in the postnatal central nervous system, perhaps involved in neuritogenic and/or synaptogenic stages, most likely playing a role in amyloid precursor protein processing andAmyloid β production.
...
1
2
3
4
5
...