Objective: Herein, the chaperonic propensities of ethanolic extract of African walnut (WNE) in Manganese-induced Parkinson-like neuropathology in the prefrontal cortex and hippocampus was investigated.

Background: The predominant accumulation of aggregated proteins is a key signature in neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases.  There has, also, been a reciprocal link between Glucocerebrosidase (GCase) activities and alpha-synuclein accumulation/aggregation; meaning, decrease in GCase activities will increase alpha-synuclein activity and an increase in GCase activities invariably reduce the alpha-synuclein accumulation. Protein misfolding and aggregation is effectively modulated by molecular chaperons recognized as heat shock proteins (HSPs) and phytochemicals have been shown to activate the expression of HSPs.

Method: 48 adult male rats weighing 185g±10g were randomly split into 6 (A – F) groups (n=8) and treated orally as follows: A-PBS (1 ml daily for 20 days), B-WNE (2 mg/kg daily for 20 days), C- WNE (4 mg/kg daily for 20 days), D-Mn (100 mg/kg daily for 20 days), E-Mn then WNE (100 mg/kg AlCl₃ daily for 20 days followed by 2 mg/kg WNE daily for subsequent 20 days), F-Mn then WNE (100 mg/kg Mn daily for 20 days followed by 4 mg/kg WNE daily for subsequent 20 days).

Results: Rats treated with WNE expressed increased levels of HSP70 and HSP90 in comparison to the Mn treated group.  GCase activity also increased significantly in WNE treated groups. Results further revealed the therapeutic tendencies of WNE against Mn toxicity by modulating oxidative redox activity, glucose bioenergetics, acetylcolinesterase activity, and proteometrics (transferrin receptor protein and total protein). Furthermore, immunohistochemical evaluation revealed reduced expression of neurofibrillary tangles, iNOS and COX-2 following WNE treatment.

Conclusion: The ethanolic extract of African Walnut induced the activation of HSPs and increased the activities of glucocerebrosidase enzyme in the corticohippocampal regions of the brain. Activated heat shock proteins suppressed neurodegenerative changes due to manganism in the treated animals. WNE was also shown to modulate cholinergic, neuroinflammatory, bioenergetics and neural redox balance in Parkinson-like neuropathology.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/chaperonic-propensities-of-african-walnut-as-a-therapeutic-target-in-manganese-induced-parkinson-like-neuropathology-in-wistar-rats/