Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Autor: Kenneth Maiese
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Akt
AMP activated protein kinase (AMPK)
apoptosis
Alzheimer′s disease
autophagy
β-cell
cancer
cardiovascular disease
caspase
CCN family
diabetes mellitus
epidermal growth factor
erythropoietin
fibroblast growth factor
forkhead transcription factors
FoxO
FRAP1
hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2)
insulin
mechanistic target of rapamycin (mTOR)
mTOR Complex 1 (mTORC1)
mTOR Complex 2 (mTORC2)
nicotinamide
nicotinamide adenine dinucleotide (NAD + )
non-communicable diseases
oxidative stress
phosphoinositide 3-kinase (PI 3-K)
programmed cell death
silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1)
sirtuin
stem cells
wingless
Wnt
Wnt1 inducible signaling pathway protein 1 (WISP1)
Neurology. Diseases of the nervous system
RC346-429
Zdroj: Neural Regeneration Research, Vol 11, Iss 3, Pp 372-385 (2016)
Druh dokumentu: article
ISSN: 1673-5374
DOI: 10.4103/1673-5374.179032
Popis: Throughout the globe, diabetes mellitus (DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), Wnt1 inducible signaling pathway protein 1 (WISP1), and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
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