Fighting neurodegeneration with rapamycin: mechanistic insights

  title={Fighting neurodegeneration with rapamycin: mechanistic insights},
  author={Jordi Bov{\'e} and Marta Mart{\'i}nez-Vicente and Miquel Vila},
  journal={Nature Reviews Neuroscience},
A growing number of studies point to rapamycin as a pharmacological compound that is able to provide neuroprotection in several experimental models of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and spinocerebellar ataxia type 3. In addition, rapamycin exerts strong anti-ageing effects in several species, including mammals. By inhibiting the activity of mammalian target of rapamycin (mTOR), rapamycin influences a variety of essential… 

It may be possible to delay the onset of neurodegenerative diseases with an immunosuppressive drug (rapamycin)

Research is needed to uncover more specific inhibitors of particular mTOR signaling pathways, and to establish realistic guidelines for treatment at early stages of neurodegenerative processes.

Staufen Impairs Autophagy in Neurodegeneration

The objective was to determine the mechanism of mTOR regulation by STAU1, which was reported to be overabundant in fibroblast cell lines from patients with spinocerebellar ataxia type 2, amyotrophic lateral sclerosis, frontotemporal degeneration, Huntington's, Alzheimer's, and Parkinson's diseases as well as animal models, and patient tissues.

Rapamycin, Autophagy, and Alzheimer's Disease.

Rapamycin enhancement of autophagy has been associated with abrogation of AD pathological processes such as clearance of Aβ and neurofibrillary tangles (NTFs) as well as reduction of tau hyper-phosphorylation and improvement of cognition, and rapamycin is emerging as a potential therapeutic compound for AD.

Mechanisms and Therapeutic Implications of GSK-3 in Treating Neurodegeneration

Three pathways that represent prominent mechanisms linking GSK-3 with neurodegenerative disorders: cytoskeleton organization, the mammalian target of rapamycin (mTOR)/autophagy axis, and mitochondria are focused on.

The Neurology of mTOR

Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease

The targeted manipulation of downstream ALP components, rather than broad autophagy stimulation, may be an attractive strategy for the development of novel pharmacological therapies in PD.

Mammalian Target of Rapamycin (mTOR) Pathways in Neurological Diseases

  • M. Wong
  • Biology, Medicine
    Biomedical journal
  • 2013
The mammalian target of rapamycin (mTOR) pathway is an essential cellular signaling pathway involved in a number of important physiological functions, including cell growth, proliferation, metabolism, protein synthesis, and autophagy, which is involved in developmental disorders and neurodegenerative diseases.

Neuroprotection in Multiple Sclerosis: A Therapeutic Approach

The current understanding of neurodegenerative processes at play in MS is reviewed and potential outcome measures and targets for neuroprotection trials are discussed.

Inhibition of the mammalian target or rapamycin (mTOR): a potential therapeutic strategy for multiple system atrophy

Multiple sources of evidence support the rationale to test if rapamycin/sirolimus can effectively block mTOR inhibition and partially block the deleterious effects of excessive insulin and IGF-1 levels, and it is tempting to hypothesize that increased activation of autophagy via m TOR inhibition may result in reduced proteinopathy-related neurodegeneration.



TOR on the brain

Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies

Various drugs and pathways inducing autophagy, which may be potential therapeutic approaches for Huntington's disease and related conditions are described.

Neuroinflammation in Parkinson's disease: a target for neuroprotection?

Neurological diseases: Targeting programmed cell death in neurodegenerative diseases

To identify potential neuroprotective targets within the PCD machinery, the expression and activity of some of its components have been altered by genetic or pharmacological means in experimental models of neurodegenerative diseases.

Rapamycin alleviates toxicity of different aggregate-prone proteins.

The studies suggest that the scope for rapamycin as a potential therapeutic in aggregate diseases may be much broader than HD or even polyglutamine diseases.

Autophagy gone awry in neurodegenerative diseases

Examples of different types of autophagic dysfunction described in common neurodegenerative disorders are presented and the prospect of exploring some of the recently identified Autophagic variants and the interactions among autphagic and non-autophagic proteolytic systems as possible future therapeutic targets are discussed.

Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease

It is shown that long-term inhibition of mTOR by rapamycin prevented AD-like cognitive deficits and lowered levels of Aβ42, a major toxic species in AD, in the PDAPP transgenic mouse model.

Rapamycin is a neuroprotective treatment for traumatic brain injury

Rapamycin Inhibits Polyglutamine Aggregation Independently of Autophagy by Reducing Protein Synthesis

It is shown that rapamycin reduces the amount of soluble polyQ protein via a modest inhibition of protein synthesis that in turn significantly reduces the formation of insoluble polyQprotein and IB formation, suggesting that rap amycin may alleviate polyQ disease pathology via its effect on global protein synthesis.