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The physiological roles of tau and Aß: implications for Alzheimer's disease pathology and therapeutics.
Kent, Sarah A; Spires-Jones, Tara L; Durrant, Claire S.
Afiliación
  • Kent SA; Translational Neuroscience PhD Programme, Centre for Discovery Brain Sciences and the UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, Scotland, UK.
  • Spires-Jones TL; Centre for Discovery Brain Sciences and the UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, Scotland, UK.
  • Durrant CS; Centre for Discovery Brain Sciences and the UK Dementia Research Institute, The University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, Scotland, UK. claire.durrant@ed.ac.uk.
Acta Neuropathol ; 140(4): 417-447, 2020 10.
Article en En | MEDLINE | ID: mdl-32728795
Tau and amyloid beta (Aß) are the prime suspects for driving pathology in Alzheimer's disease (AD) and, as such, have become the focus of therapeutic development. Recent research, however, shows that these proteins have been highly conserved throughout evolution and may have crucial, physiological roles. Such functions may be lost during AD progression or be unintentionally disrupted by tau- or Aß-targeting therapies. Tau has been revealed to be more than a simple stabiliser of microtubules, reported to play a role in a range of biological processes including myelination, glucose metabolism, axonal transport, microtubule dynamics, iron homeostasis, neurogenesis, motor function, learning and memory, neuronal excitability, and DNA protection. Aß is similarly multifunctional, and is proposed to regulate learning and memory, angiogenesis, neurogenesis, repair leaks in the blood-brain barrier, promote recovery from injury, and act as an antimicrobial peptide and tumour suppressor. This review will discuss potential physiological roles of tau and Aß, highlighting how changes to these functions may contribute to pathology, as well as the implications for therapeutic development. We propose that a balanced consideration of both the physiological and pathological roles of tau and Aß will be essential for the design of safe and effective therapeutics.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Proteínas tau / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Proteínas tau / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: Acta Neuropathol Año: 2020 Tipo del documento: Article