Naslov
Cytoskeletal changes as an alternative view on pathogenesis of Alzheimer’s disease

Autori
Šimić, Goran ; Gnjidić, Maša ; Kostović, Ivica ;

Izvornik
Periodicum biologorum (0031-5362) 100 (1998), 2; 165-173

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
abnormal phosphorylation, dystrophic neurite, neurofibrillary tangle

Sažetak
The main cytoskeletal change and the most characteristic neuropathological lesion in Alzheimer's disease (AD) is neurofibrillary degeneration. Neurofibrillary degeneration is the gradual interneuronal accumulation of paired helical filaments which consist of abnormally phosphorylated microtubule- associated protein tau. Neurofibrillary tangles, neuropil threads and senile plaque dystrophic neurites formed from paired helical filaments develop in only a few types of cortical pyramidal cells and their regional distribution correlates with the degree of dementia. First changes in both 'normal' aging and AD brains are seen in entorhinal cortex. In AD, the destructive process then spreads into the hippocampal formation and the neocortex. While most investigators still believe that beta-amyloid deposition is the central responsible factor in AD, in the last several years many authors suggest that a more satisfying pathogenetic scheme can be based on the centrality of cytoskeletal abnormality. This concept is supported by the fact that all six identified genes for AD (APP, PS-1, PS-2, APOE, CO-1 and CO-2) interact in some way with the cytoskeleton. Cytoskeletal abnormality leads to alterations of the Golgi apparatus with subsequent effects on protein processing and axoplasmic flow. The outcome is a loss of synapses and neurons followed with the disconnection syndrome and dementia. It seems that it takes 20-30 years from the earliest neuronal changes caused by light hyperphosphorylation to the development of obvious AD symptoms, because such neurons are only visible in adults over 30. The altered tau protein shown by the antibody AT8 (binds to abnormally phosphorylated Ser-202) is the earliest cytoskeleton change which eventually leads to the formation of paired helical filaments. The roles of microtubule-associated kinases and phosphatases have yet to be fully described, but may lead to identification of therapeutic targets for halting the progression of paired helical filament formation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA