Signal transduction during amyloid-β-peptide neurotoxicity: role in Alzheimer disease

摘要: Alzheimer's disease (AD) is a neurodegenerative disorder with progressive dementia accompanied by two main structural changes in the brain: intracellular protein deposits termed neurofibrillary tangles (NFT) and extracellular amyloid surrounded dystrophic neurites that constitutes senile plaques. Currently, it widely accepted beta-peptide (A beta) metabolism disbalance crucial for AD progression. A beta deposition may be enhanced molecular chaperones, including metals like copper proteins acetylcholinesterase (AChE). At neuronal level, several AD-related interact transducers of Wnt/beta-catenin signaling pathway, beta-catenin glycogen synthase kinase 3 (GSK-3 both vitro vivo studies suggest target toxicity. Accordingly, activation this lithium or Wnt ligands AD-experimental animal models primary hippocampal neurons attenuate neurotoxicity recovering levels Wnt-target gene expression survival genes such as bcl-2. On other hand, peroxisomal proliferator-activated receptor gamma (PPAR gamma) muscarinic acetylcholine (mAChR) agonists also activate they have neuroprotective effects on neurons. Our are consistent idea sustained loss function components would trigger series events, determining onset development modulation pathway through cross-talking cascades should considered possible therapeutic strategy treatment.