Tau protein and the neurofibrillary pathology of Alzheimer's disease

AbstractSynapses are the principal sites for chemical communication between neurons and are essential for performing the dynamic functions of the brain. In Alzheimer’s disease and related tauopathies, synapses are exposed to disease modified protein tau, which may cause the loss of synaptic contacts that culminate in dementia. In recent decades, structural, transcriptomic and proteomic studies suggest that Alzheimer’s disease represents a synaptic disorder. Tau neurofibrillary pathology and synaptic loss correlate well with cognitive impairment in these disorders. Moreover, regional distribution and the load of neurofibrillary lesions parallel the distribution of the synaptic loss. Several transgenic models of tauopathy expressing various forms of tau protein exhibit structural synaptic deficits. The pathological tau proteins cause the dysregulation of synaptic proteome and lead to the functional abnormalities of synaptic transmission. A large body of evidence suggests that tau protein plays a key role in the synaptic impairment of human tauopathies.

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No correlation between CSF tau protein phosphorylated at threonine 181 with neocortical neurofibrillary pathology in Alzheimer's disease

Brain ◽

10.1093/brain/awm140 ◽

2007 ◽

Vol 130 (10) ◽

pp. e82-e82 ◽

Cited By ~ 43

Author(s):

K. Buerger ◽

I. Alafuzoff ◽

M. Ewers ◽

T. Pirttila ◽

R. Zinkowski ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Neurofibrillary Pathology

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Phosphorylated tau protein as a core biomarker of Alzheimer’s disease

Pharmacopsychiatry ◽

10.1055/s-2003-825356 ◽

2004 ◽

Vol 36 (05) ◽

Author(s):

H Hampel

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Phosphorylated Tau ◽

Phosphorylated Tau Protein

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Molecular Docking Studies on Evolvulus Alsinoides Compounds Against TAU Protein in Alzheimer’s Disease

International Journal of Scientific Research ◽

10.15373/22778179/jan2014/7 ◽

2012 ◽

Vol 3 (1) ◽

pp. 21-24

Author(s):

Darsi Vanaja ◽

◽

Kuna Yellamma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Molecular Docking ◽

Tau Protein ◽

Docking Studies ◽

Molecular Docking Studies ◽

Evolvulus Alsinoides

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Targeting Tau Hyperphosphorylation via Kinase Inhibition: Strategy to Address Alzheimer's Disease

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200106125910 ◽

2020 ◽

Vol 20 (12) ◽

pp. 1059-1073 ◽

Cited By ~ 3

Author(s):

Ahmad Abu Turab Naqvi ◽

Gulam Mustafa Hasan ◽

Md. Imtaiyaz Hassan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Glycogen Synthase ◽

Paired Helical Filaments ◽

Tau Hyperphosphorylation ◽

Microtubule Stabilization ◽

Extracellular Signal

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.

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