Abstract: Provided herein are chimeric receptors, engineered cells and pharmaceutical compositions for enhancement of long-term clearance of protein aggregates in the central nervous system via phagocytosis or engulfment. Further provided herein are methods of treatment of subjects suffering from, or diagnosed with, a neurodegenerative disease by administering these receptors, modified cells, and/or pharmaceutical compositions. Administration of one or more, or a plurality of these modified cells, to a subject may provide treatment of a neurodegenerative disease such as Alzheimer's Disease (AD) or Parkinson's Disease (PD). Advantageously, the modified cells, pharmaceutical compositions, and methods of the present disclosure meet existing needs in the art by providing clearance of accumulations of protein aggregates in brain tissue in PD and AD pathologies.

Abstract: Provided herein are compositions and methods for the stable production of bioactive small peptides of interest through delivery to target cells based on the fusion of small peptides of interest to a collagen domain of a C1qTNF protein to produce a novel scaffold protein capable of multimerization. Advantageously, the fusion proteins, compositions and methods of the present disclosure meet existing needs in the art by providing for higher stable expression and longer stability of intracellular and secretable peptides of interest. Additionally, the fusion proteins, compositions and methods of the present disclosure provide for improved binding affinity of expressed receptor peptides with ligand binding partners in the target cell. Further provided herein are polynucleotide constructs encoding the described fusion proteins and recombinant adeno-associated viral particles comprising these polynucleotides.