Paper Report for: Goswami_2020_Brain.Res.Bull_165_108
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Title: Involvement of endoplasmic reticulum stress in amyloid beta ((1-42))-induced Alzheimer's like neuropathological process in rat brain Goswami P, Afjal MA, Akhter J, Mangla A, Khan J, Parvez S, Raisuddin S Ref: Brain Research Bulletin, 165:108, 2020 : PubMed
Amyloid-beta (Abeta) accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated in aetiology of neurodegenerative disorders. We studied the involvement of ER stress in Abeta-induced neuronal degeneration in rat brain to correlate it with cellular and molecular modifications in Abeta-induced Alzheimer's like neuropathological process. Abeta ((1-42)) (5 microg) was administered by bilateral intracerebroventricular (icv) injection in the brain of adult male Wistar rats. Acetylcholinesterase (AChE) activity and histological alterations were observed in different brain regions. ER stress-associated proteins- glucose regulated protein-78 (GRP78), eukaryotic translation initiation factor-2alpha (eIF2alpha) and growth arrest and DNA damage-inducible protein-153 (GADD153), neuronal marker- microtubule associated protein-2 (MAP-2) and microglial protein- ionized calcium binding adaptor molecule-1 (Iba-1) were measured by western blot. Reduced glutathione (GSH), nitrite level and levels of caspase-12 and caspase-3 were also measured. ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneally, ip) was used to assess the specific role of ER stress. Abeta ((1-42))-induced increase in AChE activity, GRP78 and GADD protein levels, dephosphorylation of eIF2-alpha and caspase-12 and caspase-3 levels and decrease in GSH and MAP-2 levels were attenuated by salubrinal. Increase in Iba-1 protein and nitrite levels after Abeta ((1-42)) administration were partially attenuated by salubrinal. Abeta ((1-42))-induced histological alterations were correlated with findings of ER stress. Results of present study implicate ER stress as a potential molecular mechanism in Abeta-induced Alzheimer's like neuropathology which could serve as surrogate biomarker for study of AD progression and efficacy of therapeutic interventions for AD management.
        
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Goswami P, Afjal MA, Akhter J, Mangla A, Khan J, Parvez S, Raisuddin S (2020) Involvement of endoplasmic reticulum stress in amyloid beta ((1-42))-induced Alzheimer's like neuropathological process in rat brain Brain Research Bulletin165: 108-117
Goswami P, Afjal MA, Akhter J, Mangla A, Khan J, Parvez S, Raisuddin S (2020) Brain Research Bulletin165: 108-117