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


ABSTRACT: 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, ?-synuclein, amyloid-? levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on ?-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.

SUBMITTER: Clark IA 

PROVIDER: S-EPMC6151331 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Clark I A IA   Vissel B B  

British journal of pharmacology 20180906 20


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 effect  ...[more]

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