Molecular determinants of paired helical filament assembly and its therapeutic implications in Alzheimer's disease

Autor:	Raúl Mena, Claude Michel Wischik, Charles R. Harrington
Rok vydání:	1995
Předmět:	Amyloidosis Tau protein Cell Human brain Biology medicine.disease Protein filament Psychiatry and Mental health Tubulin medicine.anatomical_structure mental disorders biology.protein medicine Axoplasmic transport Phosphorylation Neuroscience
Zdroj:	International Review of Psychiatry. 7:299-338
ISSN:	1369-1627 0954-0261
DOI:	10.3109/09540269509022985
Popis:	SummaryStudies of Alzheimer's disease have pointed to loss of the normal microtubule associated protein tau and accumulation of pathological paired helical filaments as strong discriminators for cognitive impairment. The most likely explanation is that the redistribution of tau protein into PHFs is associated with a failure of axonal transport in cortico-cortical association circuits through failure to maintain axonal tubulin in the polymerized state within pyramidal cells. Current understanding of and attempts to translate the key pathogenetic steps in tau pathology as they occur in the human brain are reviewed Although the phosphorylation hypothesis has dominated the application of molecular and cell biological methods, there are substantial difficulties with this account when it has been tested in clinico-pathological studies. The present review develops a more pragmatic view of PHF assembly, that it is in principle an amyloidosis, since more than 80% of the tau protein found PHFs is in the form of det...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::a0c187fc8a976f8ef31f8572d76e372b https://doi.org/10.3109/09540269509022985 Zobrazit plný text záznamu Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.