PMID- 38170440
OWN - NLM
STAT- Publisher
LR  - 20240103
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
DP  - 2024 Jan 3
TI  - Guggulsterone Selectively Modulates STAT-3, mTOR, and PPAR-Gamma Signaling in a 
      Methylmercury-Exposed Experimental Neurotoxicity: Evidence from CSF, Blood 
      Plasma, and Brain Samples.
LID - 10.1007/s12035-023-03902-x [doi]
AB  - Amyotrophic lateral sclerosis (ALS) is a paralytic disease that damages the brain 
      and spinal cord motor neurons. Several clinical and preclinical studies have 
      found that methylmercury (MeHg(+)) causes ALS. In ALS, MeHg(+)-induced 
      neurotoxicity manifests as oligodendrocyte destruction; myelin basic protein 
      (MBP) deficiency leads to axonal death. ALS development has been connected to an 
      increase in signal transducer and activator of transcription-3 (STAT-3), a 
      mammalian target of rapamycin (mTOR), and a decrease in peroxisome 
      proliferator-activated receptor (PPAR)-gamma. Guggulsterone (GST), a 
      plant-derived chemical produced from Commiphorawhighitii resin, has been found to 
      protect against ALS by modulating these signaling pathways. Vitamin D(3) 
      (VitD(3)) deficiency has been related to oligodendrocyte precursor cells (OPC) 
      damage, demyelination, and white matter deterioration, which results in motor 
      neuron death. As a result, the primary goal of this work was to investigate the 
      therapeutic potential of GST by altering STAT-3, mTOR, and PPAR-gamma levels in a 
      MeHg(+)-exposed experimental model of ALS in adult rats. The GST30 and 60 mg/kg 
      oral treatments significantly improved the behavioral, motor, and cognitive 
      dysfunctions and increased remyelination, as proven by the Luxol Fast Blue stain 
      (LFB), and reduced neuroinflammation as measured by histological examinations. 
      Furthermore, the co-administration of VitD3 exhibits moderate efficacy when 
      administered in combination with GST60. Our results show that GST protects 
      neurons by decreasing STAT-3 and mTOR levels while increasing PPAR-gamma protein 
      levels in ALS rats.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Kumar, Sumit
AU  - Kumar S
AD  - Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An 
      Autonomous College), NAAC Accredited "A" Grade College, GT Road, Ghal-Kalan, 
      Moga, 142 001, Punjab, India.
AD  - IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.
FAU - Mehan, Sidharth
AU  - Mehan S
AUID- ORCID: 0000-0003-0034-835X
AD  - Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An 
      Autonomous College), NAAC Accredited "A" Grade College, GT Road, Ghal-Kalan, 
      Moga, 142 001, Punjab, India. sidh.mehan@gmail.com.
AD  - IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India. 
      sidh.mehan@gmail.com.
FAU - Khan, Zuber
AU  - Khan Z
AD  - Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An 
      Autonomous College), NAAC Accredited "A" Grade College, GT Road, Ghal-Kalan, 
      Moga, 142 001, Punjab, India.
AD  - IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.
FAU - Das Gupta, Ghanshyam
AU  - Das Gupta G
AD  - IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India.
AD  - Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India.
FAU - Narula, Acharan S
AU  - Narula AS
AD  - Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC, 27516, USA.
LA  - eng
GR  - DST-SERB/DST-SERB, Govt. of India; Core Research Grant/
GR  - Govt. of India; Core Research Grant - CRG/2021/001009/DST-SERB, Govt. of India; 
      Core Research Grant/
PT  - Journal Article
DEP - 20240103
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
SB  - IM
OTO - NOTNLM
OT  - Amyotrophic lateral sclerosis
OT  - JAK/STAT-3
OT  - Methylmercury
OT  - Neuroprotection
OT  - mTOR, PPAR-gamma, Demyelination, Oligodendrocytes
EDAT- 2024/01/04 01:18
MHDA- 2024/01/04 01:18
CRDT- 2024/01/03 12:57
PHST- 2023/10/11 00:00 [received]
PHST- 2023/12/14 00:00 [accepted]
PHST- 2024/01/04 01:18 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 12:57 [entrez]
AID - 10.1007/s12035-023-03902-x [pii]
AID - 10.1007/s12035-023-03902-x [doi]
PST - aheadofprint
SO  - Mol Neurobiol. 2024 Jan 3. doi: 10.1007/s12035-023-03902-x.