Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra

Sigma-1 receptor (σ1R) is expressed in dopaminergic neurons of substantia nigra (SN). Here, we show that σ1R knockout (σ1R-/-) mice, at 6 to 12 months of age, appeared age-related loss of dopaminergic neurons and decline of motor coordination. Levels of α-synuclein (αSyn) oligomers and fibrillar αSyn in SN of σ1R-/- mice were age-dependently increased without the changes in αSyn monomers. The phosphorylation of αSyn monomers or oligomers in dopaminergic neurons was enhanced in σ1R-/- mice. Levels of phosphorylated eIF2a and CHOP expression were elevated in σ1R-/- mice with decline of proteasome activity.📍


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