Reduced autophagy leads to reduction of GABA-A receptors
Mechanistically, excess p62 binds and sequesters GABAA receptor-associated protein (GABARAP), an adapter that regulates endocytic GABAAR trafficking, leading to limited availability of GABARAP for surface presentation of GABAARs and selective down-modulation of GABA neurotransmission in Ulk2þ/ pyramidal neurons. (R1)
P62 here, is a protein that binds to other proteins that needs to be degraded during autophagy. When autophagy is not happening, there is accumulation of p62, which can bind to many proteins/enzymes, causing changes in cellular functions.
This paper describes that accumulated p62 binds to a protein that regulates transport of GABA-A receptors to the membrane. This leads to reduction of GABA-A receptors on the cellular surface.
I suspect this might be related to the root cause of TS, where GABAergic neurotransmission is not sufficient.