A critical appraisal of tau-targeting therapies for primary and secondary tauopathies.
Alzheimers Dement
; 18(5): 1008-1037, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-34533272
ABSTRACT
INTRODUCTION:
Primary tauopathies are neurological disorders in which tau protein deposition is the predominant pathological feature. Alzheimer's disease is a secondary tauopathy with tau forming hyperphosphorylated insoluble aggregates. Tau pathology can propagate from region to region in the brain, while alterations in tau processing may impair tau physiological functions.METHODS:
We reviewed literature on tau biology and anti-tau drugs using PubMed, meeting abstracts, and ClnicalTrials.gov.RESULTS:
The past 15 years have seen >30 drugs interfering with tau aggregation, processing, and accumulation reaching the clinic. Initial results with tau aggregation inhibitors and anti-tau monoclonal antibodies have not shown clinical efficacy.DISCUSSION:
The reasons for these clinical failures are unclear but could be linked to the clearing of physiological forms of tau by non-specific drugs. Research is now concentrating efforts on developing reliable translational animal models and selective compounds targeting specific tau epitopes, neurotoxic tau aggregates, and post-translational tau modifications.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tauopatias
/
Doença de Alzheimer
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article