PMID- 37907134
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 961
DP  - 2023 Dec 15
TI  - Repurposing and clinical attributes of antidiabetic drugs for the treatment of 
      neurodegenerative disorders.
PG  - 176117
LID - S0014-2999(23)00631-3 [pii]
LID - 10.1016/j.ejphar.2023.176117 [doi]
AB  - The risk of neurodegeneration was found to be increased among people with type 2 
      diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's 
      disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are 
      considered neurodegenerative diseases and can be characterized by progressive 
      loss of neurons. The deficiency of insulin, impaired signaling, and its 
      resistance lead to alteration in the neuronal functioning of the brain. Insulin 
      degrading enzyme (IDE) plays a significant role in the amyloid beta metabolism, 
      aggregation, and deposition of misfolded proteins in the brain's hippocampal and 
      cortical neuronal regions. The insulin signaling via IP3 activation upregulates 
      the IDE and could be a promising approach to regulate neurodegeneration. The 
      repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, 
      thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 
      (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy 
      to treat neurodegeneration via modulating insulin signaling, insulin resistance, 
      IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile 
      and neuroinflammation in the brain. Antidiabetic medications reduce the risk of 
      neuroinflammation, oxidative stress, and Abeta deposition by enhancing their 
      clearance rate. The downregulation of IDE alters the degradation of Abeta monomers 
      in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK 
      pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced 
      mice model. Thus, the primary intention of this review is to explore the link 
      between T2DM and neurodegenerative disorders, and the possible role of various 
      antidiabetic drugs in the management of neurodegenerative disorders.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Birajdar, Swapnali Vasant
AU  - Birajdar SV
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER) Raebareli, Lucknow, 226002, Uttar Pradesh, India.
FAU - Mazahir, Farhan
AU  - Mazahir F
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER) Raebareli, Lucknow, 226002, Uttar Pradesh, India.
FAU - Alam, Md Imtiyaz
AU  - Alam MI
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER) Raebareli, Lucknow, 226002, Uttar Pradesh, India.
FAU - Kumar, Amit
AU  - Kumar A
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER) Raebareli, Lucknow, 226002, Uttar Pradesh, India.
FAU - Yadav, Awesh K
AU  - Yadav AK
AD  - Department of Pharmaceutics, National Institute of Pharmaceutical Education and 
      Research (NIPER) Raebareli, Lucknow, 226002, Uttar Pradesh, India. Electronic 
      address: awesh.yadav@niperraebareli.edu.in.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20231030
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Amyloid beta-Peptides/metabolism
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Drug Repositioning
MH  - Neuroinflammatory Diseases
MH  - *Alzheimer Disease/drug therapy
MH  - Insulin/metabolism
MH  - *Metformin/pharmacology
OTO - NOTNLM
OT  - AMPK/mTOR/BACE1
OT  - Antidiabetic drugs
OT  - Insulin degrading enzyme (IDE)
OT  - Insulin resistance
OT  - Neurodegenerative disorders
OT  - Oxidative stress
COIS- Declaration of competing interest All authors declare no competing interests with 
      anyone or other organizations.
EDAT- 2023/11/01 00:42
MHDA- 2023/12/17 09:43
CRDT- 2023/10/31 20:16
PHST- 2023/07/03 00:00 [received]
PHST- 2023/10/03 00:00 [revised]
PHST- 2023/10/12 00:00 [accepted]
PHST- 2023/12/17 09:43 [medline]
PHST- 2023/11/01 00:42 [pubmed]
PHST- 2023/10/31 20:16 [entrez]
AID - S0014-2999(23)00631-3 [pii]
AID - 10.1016/j.ejphar.2023.176117 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Dec 15;961:176117. doi: 10.1016/j.ejphar.2023.176117. Epub 
      2023 Oct 30.