Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0153640 (
Cerebellum
)
1,777
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
This short review analyses the possible molecular events linking a general program of death such as apoptosis to highly specific intracellular pathways involving the function and degradation of two proteins--tau and amyloid precursor protein--which in their aggregated state constitute the hallmark of Alzheimer disease. By surveying the recent studies carried out in 'in vitro' neuronal cultures--with special emphasis to cerebellar granule neurons--the apparent correlation between onset of apoptosis, tau cleavage with formation of potential toxic fragments, and activation of an amyloidogenic route are discussed. Within this framework, proteasomes seem to play a crucial role upstream of the proteolytic cascade involving
calpain
(s) and caspase(s) by contributing to tau and amyloid precursor protein-altered breakdown and consequent tendency to aggregation of their degradation fragments. Thus, apoptotic death due to altered supply of anti apoptotic agents, neurotrophic factors, deafferentiation or other causes, may constitute a major trigger of the onset of Alzheimer disease.
Cerebellum
2003
PMID:In vitro cultured neurons for molecular studies correlating apoptosis with events related to Alzheimer disease. 1496 86