Abstract
Insulin resistance is common in type 2 diabetes mellitus (T2DM), neurodegenerative diseases, cardiovascular diseases, kidney diseases, and polycystic ovary syndrome. Impairment in insulin signaling pathways, such as the PI3K/Akt/mTOR pathway, would lead to insulin resistance. It might induce the synthesis and deposition of advanced glycation end products (AGEs), reactive oxygen species, and reactive nitrogen species, resulting in stress, protein misfolding, protein accumulation, mitochondrial dysfunction, reticulum function, and metabolic syndrome dysregulation, inflammation, and apoptosis. It plays a huge role in various neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and Amyloid lateral sclerosis. In this review, we intend to focus on the possible effect of insulin resistance in the progression of neurodegeneration via the impaired P13K/Akt/mTOR signaling pathway, AGEs, and receptors for AGEs.
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Data Availability
Data sharing is not applicable for this study as no datasets are genarated or analyzed in the current study.
Abbreviations
- 4E BP1:
-
Eukaryotic translation initiation factor 4E (elF4E)-binding protein 1
- AD:
-
Alzheimer’s disease
- AGEs:
-
Advances glycation end products
- ALS:
-
Amyloid lateral sclerosis
- AKT:
-
AK strain transforming
- AMPK:
-
AMP-activated protein kinase
- APP:
-
Amyloid precursor protein
- APS:
-
Adaptor protein with Pleckstrin homology and Src homology 2 domains
- ATP:
-
Adenosine triphosphate
- ATG:
-
Autophagy-related gene
- Bax:
-
Bcl-2 associated X protein
- BBB:
-
Blood–Brain Barrier
- BNIP 3:
-
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
- CML:
-
Nε-carboxy-methyl-lysine
- c-Myc:
-
Master Regulator of Cell Cycle Entry and Proliferative Metabolism
- Cpd38:
-
6-(2,4-difluorophenoxy)-5-((ethylmethyl)pyridine-3-yl)-8-methylpyrrolo[1,2-a] pyrazin-1(2H)-one
- CREB:
-
cAMP-responsive element-binding protein
- CVD:
-
Cardiovascular diseases
- DEPTOR:
-
DEP domain-containing interacting protein
- DPP4:
-
Dipeptidyl-peptidase 4
- DM:
-
Diabetes mellitus
- ERK:
-
Extracellular signal-regulated kinase
- FOX O:
-
Forehead box O transcription factor
- FRK:
-
Fyn-related kinase
- FUS/TLS:
-
Fused in sarcoma/translocated in liposarcoma
- GLP 1:
-
Glucagon-like polypeptide 1
- GABA:
-
Gama-aminobutyric acid
- GLUT:
-
Glucose transporter
- GPCR:
-
G protein-coupled receptor
- GRB:
-
Growth factor receptor-bound protein
- GSK:
-
Glycogen synthase kinase
- HD:
-
Huntington’s disease
- HIF1a:
-
Hypoxia-inducible Factor-1a
- HTT:
-
Huntington protein
- IGF:
-
Insulin growth factor
- IL:
-
Interleukin
- IR:
-
Insulin receptor
- IRS:
-
Insulin receptor substrate
- JNK:
-
Jun kinase
- MAPK:
-
Mitogen-activated protein kinase
- MELAS:
-
Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes
- MLST8:
-
Mammalian lethal with SEC18 protein 8
- mSIN- mLST 1- mTOR:
-
Mechanistic/mammalian target of rapamycin
- NADPH:
-
Mitogen-activated protein kinase
- NF κb:
-
Nuclear factor kappa-light chain-enhancer of activated B cells
- Nrf:
-
Nuclear factor κ-light-chain-enhancer of activated B cell
- NMDA:
-
N-methyl-D-aspartate
- PD:
-
Parkinson’s disease
- PDK:
-
Phosphoinositide-dependent Protein Kinase
- Pkc:
-
Protein Kinase C
- PI3K:
-
Phosphatidyl inositol 3 phosphate kinase
- PIP3:
-
Phosphatidyl inositol 3,4,5 triphosphate
- PINK:
-
PTEN putative kinase 1
- PKB:
-
Protein kinase B
- PTEN:
-
Phosphatase and tensin homolog
- PTP1B:
-
Protein-tyrosine Phosphatase 1B
- PP-242:
-
mTOR inhibitor
- PPAR:
-
Peroxisome proliferator-activated receptor
- PRAS 8:
-
Protease-activated receptors 8
- RTK:
-
Receptor tyrosine kinase
- RAGE:
-
Receptor for AGEs
- RAPTOR:
-
Regulatory associated protein of mTOR
- RHEB:
-
Ras homologous enriched in the brain
- RICTOR:
-
Rapamycin-insensitive companion of mTOR
- ROS:
-
Reactive oxygen species
- RNS:
-
Reactive nitrogen species
- RXR:
-
Retinoid transcription factor
- SREBP1:
-
Sterol regulatory element-binding transcription factor 1
- SGK:
-
Serine/threonine-protein kinase
- SR:
-
Scavenger receptor
- S6K:
-
Ribosomal s6 kinase
- SOXS3:
-
Suppressor of cytokine signaling 3
- SOD1:
-
Superoxide dismutase 1
- STAT:
-
Signal transducer and activator of transcription
- SHcA:
-
SHC transforming protein 1
- TDP-43:
-
TAR DNA-binding protein 43
- TSC:
-
Tuberous sclerosis proteins
- TNF:
-
Tumor necrosis factor
- VEGF:
-
Vascular endothelial growth factor
- Wnt:
-
Wingless-related integration site
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Ramasubbu, K., Devi Rajeswari, V. Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review. Mol Cell Biochem 478, 1307–1324 (2023). https://doi.org/10.1007/s11010-022-04587-x
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DOI: https://doi.org/10.1007/s11010-022-04587-x