NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy
NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy
Alzheimer’s disease (AD) is a devastating neurodegenerative disease causing irreversible cognitive decline in the elderly. There is no disease-modifying therapy for this condition and the mechanisms underpinning neuronal dysfunction and neurodegeneration are unclear. Compromised cytoskeletal integrity within neurons is reported in AD. This is believed to result from loss-of-function of the microtubule-associated protein tau, which becomes hyper-phosphorylated and deposits into neurofibrillary tangles in AD. We have developed a Drosophila model of tauopathy in which abnormal human tau mediates neuronal dysfunction characterised by microtubule destabilisation, axonal transport disruption, synaptic defects and behavioural impairments. Here we show that a microtubule-stabilising drug, NAPVSIPQ (NAP), prevents as well as reverses these phenotypes even after they have become established. Moreover, it does not alter abnormal tau levels indicating that it by-passes toxic tau altogether. Thus, microtubule stabilisation is a disease-modifying therapeutic strategy protecting against tau-mediated neuronal dysfunction, which holds great promise for tauopathies like AD.
alzheimer’s disease, axonal transport, drosophila, microtubules, NAP (davunetide)
834-842
Quraishe, S.
cfc3aed4-f120-41aa-9127-0fc26c657ad2
Cowan, C.M.
db1ae417-5715-4374-82dc-840fb75a2c6c
Mudher, A.
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
16 April 2013
Quraishe, S.
cfc3aed4-f120-41aa-9127-0fc26c657ad2
Cowan, C.M.
db1ae417-5715-4374-82dc-840fb75a2c6c
Mudher, A.
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Quraishe, S., Cowan, C.M. and Mudher, A.
(2013)
NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy.
Molecular Psychiatry, 18, .
(doi:10.1038/mp.2013.32).
(PMID:23587881)
Abstract
Alzheimer’s disease (AD) is a devastating neurodegenerative disease causing irreversible cognitive decline in the elderly. There is no disease-modifying therapy for this condition and the mechanisms underpinning neuronal dysfunction and neurodegeneration are unclear. Compromised cytoskeletal integrity within neurons is reported in AD. This is believed to result from loss-of-function of the microtubule-associated protein tau, which becomes hyper-phosphorylated and deposits into neurofibrillary tangles in AD. We have developed a Drosophila model of tauopathy in which abnormal human tau mediates neuronal dysfunction characterised by microtubule destabilisation, axonal transport disruption, synaptic defects and behavioural impairments. Here we show that a microtubule-stabilising drug, NAPVSIPQ (NAP), prevents as well as reverses these phenotypes even after they have become established. Moreover, it does not alter abnormal tau levels indicating that it by-passes toxic tau altogether. Thus, microtubule stabilisation is a disease-modifying therapeutic strategy protecting against tau-mediated neuronal dysfunction, which holds great promise for tauopathies like AD.
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Accepted/In Press date: 28 January 2013
Published date: 16 April 2013
Keywords:
alzheimer’s disease, axonal transport, drosophila, microtubules, NAP (davunetide)
Organisations:
Biomedicine
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Local EPrints ID: 348388
URI: http://eprints.soton.ac.uk/id/eprint/348388
ISSN: 1359-4184
PURE UUID: 7570b2a0-9f09-410e-9ea8-e711d6de86bb
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Date deposited: 13 Feb 2013 11:30
Last modified: 15 Mar 2024 03:25
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C.M. Cowan
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