Author/Editor		Mohorko, Nina; Bresjanac, Mara
Title		Tau protein and human tauopathies: an overwiev
Translated title		Protein tau in humane taupatije: pregled področja
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 77, št. Suppl 2
Publication year		2008
Volume		str. II-35-41
Language		eng
Abstract		The growing knowledge of the molecular mechanisms of neurodegenerative diseases is unveiling their common characteristics, enabling their classification according to the pathologically changed protein that aggregates in the diseased central nervous system. Due to aggregation of hyperphosphorilated microtubule associated protein tau in a large group of neurodegenerative diseases, mostly dementias, these diseases have been collectively called tauopathies. In the healthy adult brain, tau protein is found in six isoforms that contain either three or four microtubule-binding domains, which divides them in two groups, accordingly. In the pathological tau filaments, all six isoforms can be found, although their representation in the filaments varies among the diseases, as does the structure of the filaments, which can be paired helical, straight or random coiled. This allows for the classification of tauopathies into five classes, according to the tau isoforms composition and structure of filaments. The filaments aggregate intracellularly, forming the so-called fibrillary tau inclusions (FTI). Today, the accurate diagnosis of tauopathies is possible only post mortem, when the spread of FTI across the brain is observed. The form and distribution of FTI differs among the diseases. They are detected by several neuropathological techniques, which differ in their efficacy to label tangles from different diseases. The causes for this differential labelling are still not understood. There is no cure for tauopathies, but better efficacy of some drugs that may slow down the cognitive decline in the early stages of the diseases and the need for monitoring the drug effects are calling for early pre mortem diagnostic tools. (Abstract truncated at 2000 characters)
Summary		Odkrivanje molekularnih mehanizmov nevrodegenerativnih bolezni razkriva njihove skupne značilnosti. To omogoča njihovo klasifikacijo glede na patološko spremenjeni protein, ki agregira v bolnem živčevju. Pri veliki skupini nevrodegenerativnih bolezni ‐ gre predvsem za demence ‐ se odlaga z mikrotubuli povezani protein tau; zato to skupino bolezni poimenujemo taupatije. V možganih odraslega je tau prisoten v šestih izoformah, ki imajo bodisi tri bodisi štiri domene za vezavo na mikrotubule. To jih deli na dve skupini. V patoloških filamentih tau je lahko prisotnih vseh šest izoform, vendar se njihova zastopanost od bolezni do bolezni razlikuje. Prav tako se med boleznimi razlikuje tudi struktura filamentov, ki so lahko parno-helikalni, ravni ali naključno zviti. Filamenti se odlagajo znotraj celic in tvorijo tako imenovane fibrilarne inkluzije tau. Na podlagi zastopanosti izoform in oblike odlagajočih se filamentov delimo taupatije v pet razredov. Natančna diagnoza taupatij je mogoča šele po smrti, ko opazujemo razširjenost fibrilarnih inkluzij tau v možganih. Njihova oblika in razporeditev po možganih se med boleznimi razlikujeta. Fibrilarne inkluzije tau zaznamo z različnimi nevropatološkimi tehnikami, ki različno uspešno označijo inkluzije v različnih boleznih. Vzroka za različno označevanje še ne poznamo. Za taupatije še nimamo zdravila, toda nekatera zdravila lahko upočasnijo odlaganje tau v zgodnjih fazah bolezni. Pravočasna prepoznava bolezni in spremljanje njenega zdravljenja zahtevata zgodnja zaživljenjska diagnostična sredstva. (Izvleček prekinjen pri 2000 znakih)
Descriptors		TAU PROTEINS NEUROFIBRILLARY TANGLES DEMENTIA ALZHEIMER'S DISEASE AMYOTROPHIC LATERAL SCLEROSIS