Abstract: Provided herein are compounds of Formula I and their salts, and compositions thereof that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) and/or acetylcholinesterase (AChE) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Further disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).