Alzheimer's disease (AD) is a devastating neurodegenerative disorder with a relentless progression. AD pathogenesis is believed to be triggered by the accumulation of the amyloid-β peptide (Aβ), which is due to overproduction of Aβ and/or the failure of clearance mechanisms. Aβ self-aggregates into oligomers, which can be of various sizes, and forms diffuse and neuritic plaques in the parenchyma and blood vessels. Aβ oligomers and plaques are potent synaptotoxins, block proteasome function, inhibit mitochondrial activity, alter intracellular Ca2+ levels and stimulate inflammatory processes. Loss of the normal physiological functions of Aβ is also thought to contribute to neuronal dysfunction. Aβ interacts with the signalling pathways that regulate the phosphorylation of the microtubule-associated protein tau. Hyperphosphorylation of tau disrupts its normal function in regulating axonal transport and leads to the accumulation of neurofibrillary tangles and toxic species of soluble tau. Furthermore, degradation of hyperphosphorylated tau by the proteasome is inhibited by the actions of Aβ. These two proteins and their associated signalling pathways therefore represent important therapeutic targets for AD.
The Poster is freely available thanks to support from Elan and Wyeth.
Amyloid-β and tau in Alzheimer's disease
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