PMID- 35064868
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20230829
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 37
IP  - 4
DP  - 2022 Apr
TI  - Epigenetic regulation and autophagy modulation debilitates insulin resistance 
      associated Alzheimer's disease condition in rats.
PG  - 927-944
LID - 10.1007/s11011-021-00846-w [doi]
AB  - Insulin resistance (IR) and accumulation of amyloid beta (Abeta) oligomers are 
      potential causative factor for Alzheimer's Disease (AD). Simultaneously, enhanced 
      clearance level of these oligomers through autophagy activation bring novel 
      insights into their therapeutic paradigm. Autophagy activation is negatively 
      correlated with mammalian target of rapamycin (mTOR) and dysregulated mTOR level 
      due to epigenetic alterations can further culminate towards AD pathogenesis. 
      Therefore, in the current study we explored the neuroprotective efficacy of 
      rapamycin (rapa) and vorinostat (vori) in-vitro and in-vivo. Abeta(1-42) treated 
      SH-SY5Y cells were exposed to rapa (20 muM) and vori (4 muM) to analyse mRNA 
      expression of amyloid precursor protein (APP), brain derived neurotrophic factor 
      (BDNF), glial cell derived neurotrophic factor (GDNF), neuronal growth factor 
      (NGF), beclin-1, microtubule-associated protein 1A/1B-light chain 
      3-phosphatidylethanolamine conjugate (LC3), lysosome-associated membrane protein 
      2 (LAMP2) and microtubule associated protein 2 (MAP2). In order to develop IR 
      condition, rats were fed a high fat diet (HFD) for 8 weeks and then subjected to 
      intracerebroventricular Abeta(1-42) administration. Subsequently, their treatment 
      was initiated with rapa (1 mg/kg, i.p.) and vori (50 mg/kg, i.p.) once daily for 
      28 days. Morris water maze was performed to govern cognitive impairment followed 
      by sacrification for subsequent mRNA, biochemical, western blot and histological 
      estimations. For all the measured parameters, a significant improvement was 
      observed amongst the combination treatment group in contrast to that of the HFD + 
      Abeta(1-42) group and that of the groups treated with the drugs alone. Outcomes of 
      the present study thus suggest that combination therapy with rapa and vori 
      provide a prospective therapeutic approach to ameliorate AD symptoms exacerbated 
      by IR.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Kakoty, Violina
AU  - Kakoty V
AUID- ORCID: 0000-0001-8366-8142
AD  - Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of 
      Technology and Science, Pilani, Pilani Campus, Rajasthan, 333031, India.
FAU - K C, Sarathlal
AU  - K C S
AUID- ORCID: 0000-0003-2297-5258
AD  - Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of 
      Technology and Science, Pilani, Pilani Campus, Rajasthan, 333031, India.
FAU - Dubey, Sunil Kumar
AU  - Dubey SK
AUID- ORCID: 0000-0002-7554-3232
AD  - Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of 
      Technology and Science, Pilani, Pilani Campus, Rajasthan, 333031, India.
AD  - R&D Healthcare Division, Emami Ltd., Kolkatta, 700107, India.
FAU - Yang, Chih-Hao
AU  - Yang CH
AUID- ORCID: 0000-0002-8354-7874
AD  - Department of Pharmacology, Taipei Medical University, Taipei, 110, Taiwan.
FAU - Marathe, Sandhya Amol
AU  - Marathe SA
AUID- ORCID: 0000-0002-7828-5478
AD  - Department of Biological Sciences, Birla Institute of Technology and Science, 
      Pilani, Pilani Campus, Rajasthan, 333031, India.
FAU - Taliyan, Rajeev
AU  - Taliyan R
AUID- ORCID: 0000-0003-2147-2990
AD  - Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of 
      Technology and Science, Pilani, Pilani Campus, Rajasthan, 333031, India. 
      rajeev.taliyan@pilani.bits-pilani.ac.in.
LA  - eng
PT  - Journal Article
DEP - 20220122
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Autophagy
MH  - Epigenesis, Genetic
MH  - *Insulin Resistance/physiology
MH  - Mammals/metabolism
MH  - RNA, Messenger
MH  - Rats
MH  - Sirolimus/therapeutic use
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Autophagy
OT  - Histone deacetylase inhibitor
OT  - Insulin resistance
OT  - Rapamycin
OT  - Vorinostat
EDAT- 2022/01/23 06:00
MHDA- 2022/04/29 06:00
CRDT- 2022/01/22 12:06
PHST- 2021/04/27 00:00 [received]
PHST- 2021/09/23 00:00 [accepted]
PHST- 2022/01/23 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2022/01/22 12:06 [entrez]
AID - 10.1007/s11011-021-00846-w [pii]
AID - 10.1007/s11011-021-00846-w [doi]
PST - ppublish
SO  - Metab Brain Dis. 2022 Apr;37(4):927-944. doi: 10.1007/s11011-021-00846-w. Epub 
      2022 Jan 22.