%0 Journal Article
%T 5-Phenyl valeric acid attenuates α-synuclein aggregation and endoplasmic reticulum stress in rotenone-induced Parkinson's disease rats: A molecular mechanistic study.
%A Kaur N
%A Singh R
%A Dhingra N
%A Kaur T
%J Biochem Pharmacol
%V 226
%N 0
%D 2024 08 7
%M 38852645
%F 6.1
%R 10.1016/j.bcp.2024.116343
%X The abnormal accumulation of fibrillar α-synuclein in the substantia nigra contributes to Parkinson's disease (PD). Chemical chaperones like 4-phenyl butyric acid (4PBA) show neuroprotective potential, but high doses are required. A derivative, 5-phenyl valeric acid (5PVA), has reported therapeutic potential for PD by reducing Pael-R expression. This study assessed 5PVA's efficacy in PD animals and its molecular mechanism. In vitro studies revealed 5PVA's anti-aggregation ability against alpha-synuclein and neuroprotective effects on SHSY5Y neuroblastoma cells exposed to rotenone. PD-like symptoms were induced in SD rats with rotenone, followed by 5PVA treatment at 100 mg/kg and 130 mg/kg. Behavioral analysis showed significant improvement in memory and motor activity with 5PVA administration. Histopathological studies demonstrated normal neuronal histoarchitecture in mid-brain tissue sections of 5PVA-treated animals compared to the PD group. mRNA studies revealed significant suppression in the expression of various protein folding and heat-shock protein markers in the 5PVA-treated group. In conclusion, 5PVA, with its anti-aggregation ability against alpha-synuclein, acts as a chemical chaperone, showing potential as a therapeutic candidate for PD treatment.