Anti–Na ⁺ /K ⁺ -ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na ⁺ /K ⁺ -ATPase α1–dependent autophagy

Abstract

) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein-induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

Topics & Concepts