Roles of tau protein in health and disease
#MMPMID28386764
Guo T
; Noble W
; Hanger DP
Acta Neuropathol
2017[May]; 133
(5
): 665-704
PMID28386764
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Tau is well established as a microtubule-associated protein in neurons. However,
under pathological conditions, aberrant assembly of tau into insoluble aggregates
is accompanied by synaptic dysfunction and neural cell death in a range of
neurodegenerative disorders, collectively referred to as tauopathies. Recent
advances in our understanding of the multiple functions and different locations
of tau inside and outside neurons have revealed novel insights into its
importance in a diverse range of molecular pathways including cell signalling,
synaptic plasticity, and regulation of genomic stability. The present review
describes the physiological and pathophysiological properties of tau and how
these relate to its distribution and functions in neurons. We highlight the
post-translational modifications of tau, which are pivotal in defining and
modulating tau localisation and its roles in health and disease. We include
discussion of other pathologically relevant changes in tau, including mutation
and aggregation, and how these aspects impinge on the propensity of tau to
propagate, and potentially drive neuronal loss, in diseased brain. Finally, we
describe the cascade of pathological events that may be driven by tau
dysfunction, including impaired axonal transport, alterations in synapse and
mitochondrial function, activation of the unfolded protein response and defective
protein degradation. It is important to fully understand the range of neuronal
functions attributed to tau, since this will provide vital information on its
involvement in the development and pathogenesis of disease. Such knowledge will
enable determination of which critical molecular pathways should be targeted by
potential therapeutic agents developed for the treatment of tauopathies.
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