Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases

Clark, IA; Vissel, B

Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases

Clark, IA Vissel, B

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Publication Type:: Journal Article
Citation:: British Journal of Pharmacology, 2018, 175 (20), pp. 3859 - 3875
Issue Date:: 2018-10-01

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Field	Value	Language
dc.contributor.author	Clark, IA	en_US
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050	en_US
dc.date.available	2018-07-23	en_US
dc.date.issued	2018-10-01	en_US
dc.identifier.citation	British Journal of Pharmacology, 2018, 175 (20), pp. 3859 - 3875	en_US
dc.identifier.issn	0007-1188	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132479
dc.description.abstract	© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1083569
dc.relation.ispartof	British Journal of Pharmacology	en_US
dc.relation.isbasedon	10.1111/bph.14471	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Neurodegenerative Diseases	en_US
dc.subject.mesh	Insulin Resistance	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Apolipoproteins E	en_US
dc.subject.mesh	tau Proteins	en_US
dc.subject.mesh	Phosphorylation	en_US
dc.subject.mesh	alpha-Synuclein	en_US
dc.subject.mesh	Amyloid beta-Peptides	en_US
dc.title	Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases	en_US
dc.type	Journal Article
utslib.citation.volume	20	en_US
utslib.citation.volume	175	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	20	en_US
pubs.publication-status	Published	en_US
pubs.volume	175	en_US

Abstract:

© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases. Therapeutic advances being tested, and arguably useful for a number of the neurodegenerative diseases, include a reduction of excess cerebral TNF, whether directly, with a specific anti-TNF biological agent such as etanercept via Batson's plexus, or indirectly via surgically implanting stem cells. Inhaled salbutamol also warrants investigating further across the neurodegenerative disease spectrum. It is now timely to integrate this range of new information across the neurodegenerative disease spectrum, rather than keep seeing it through the lens of individual disease states.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/132479