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Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies

Silva, M Catarina ; Haggarty, Stephen J

International journal of molecular sciences, 2020-11, Vol.21 (23), p.8948 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies
Autor: Silva, M Catarina ; Haggarty, Stephen J
Assuntos: Adults ; aggregation ; Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer Disease - pathology ; Alzheimer's disease ; Brain - metabolism ; Brain - pathology ; Brain research ; Cell death ; Cell Death - genetics ; Clinical trials ; Cytoskeleton - genetics ; Cytoskeleton - pathology ; Dementia ; Dementia disorders ; Disease ; Drug development ; Etiology ; Filaments ; Frontotemporal dementia ; Frontotemporal Dementia - genetics ; Frontotemporal Dementia - metabolism ; Frontotemporal Dementia - pathology ; Humans ; Kinases ; Molecular modelling ; Mutation ; Mutation - genetics ; Neurodegeneration ; Neurofibrillary tangles ; Neurofibrillary Tangles - genetics ; Neurofibrillary Tangles - pathology ; Neuroglia - metabolism ; Neuroglia - pathology ; Neuronal-glial interactions ; Neurons - metabolism ; Neurons - pathology ; Neurotoxicity ; pathogenicity ; Pathology ; Phosphorylation ; Physiology ; Precision medicine ; Proteins ; Review ; Signal transduction ; tau ; Tau protein ; tau Proteins - genetics ; Tauopathies - genetics ; Tauopathies - pathology
É parte de: International journal of molecular sciences, 2020-11, Vol.21 (23), p.8948
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
Descrição: Tauopathies are neurodegenerative diseases characterized by the pathological accumulation of microtubule-associated protein tau (MAPT) in the form of neurofibrillary tangles and paired helical filaments in neurons and glia, leading to brain cell death. These diseases include frontotemporal dementia (FTD) and Alzheimer's disease (AD) and can be sporadic or inherited when caused by mutations in the gene. Despite an incredibly high socio-economic burden worldwide, there are still no effective disease-modifying therapies, and few tau-focused experimental drugs have reached clinical trials. One major hindrance for therapeutic development is the knowledge gap in molecular mechanisms of tau-mediated neuronal toxicity and death. For the promise of precision medicine for brain disorders to be fulfilled, it is necessary to integrate known genetic causes of disease, i.e., mutations, with an understanding of the dysregulated molecular pathways that constitute potential therapeutic targets. Here, the growing understanding of known and proposed mechanisms of disease etiology will be reviewed, together with promising experimental tau-directed therapeutics, such as recently developed tau degraders. Current challenges faced by the fields of tau research and drug discovery will also be addressed.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies

Silva, M Catarina ; Haggarty, Stephen J

Switzerland: MDPI AG

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