The invention provides compositions for increasing the clearance of protein aggregates, and pharmaceutical compositions comprising them, and methods for making and using them, including methods for accelerating protein aggregate clearance in the CNS, e.g., for treating diseases that are characterized by protein aggregation—including some degenerative neurological diseases such as Parkinson's disease. In one aspect, the compositions of the invention specifically target synuclein, beta-amyloid and/or tau protein aggregates, and the methods of the invention can be used to specifically prevent, reverse, slow or inhibit synuclein, beta-amyloid and/or tau protein aggregation. In alternative embodiments, the compositions and methods of the invention, are used to treat, prevent, reverse (partially or completely) or ameliorate (including slowing the progression of) degenerative neurological diseases related to or caused by protein aggregation, e.g., synuclein, beta-amyloid and/or tau protein aggregation. In one aspect, compositions and methods of this invention are used to treat, prevent or ameliorate (including slowing the progression of) Parkinson's disease, fronto-temporal dementia (FTD), Alzheimer's Disease (AD), Lewy body disease (LBD) and Multiple system atrophy (MSA).