Can Intrabodies Serve as Neuroprotective Therapies for Parkinson's Disease? Beginning Thoughts

Misfolded proteins and subsequent protein aggregation appears to underlie a significant fraction of neurodegenerative diseases including Parkinson's disease. One of the neuropathological hallmarks of Parkinson's disease is the presence of alpha-syn containing intracellular inclusions known as Lewy bodies and Lewy neurites. Intrabodies are antibody fragments that have been engineered to be expressed intracellularly. They can be directed towards specific target antigens present in various subcellular locations, and have shown promise in cancer, HIV, autoimmune diseases, and Huntington's disease. More recently they have been shown to modulate abnormalities caused by aggregated alpha-syn in cell culture. This mini-review mainly focuses on summarizing structural and cellular effects of intrabodies shown to have affinity for different forms of alpha-synuclein (monomeric, oligomeric and fibrillar), as well as those exhibiting affinity for particular residues of alpha-synuclein (e.g., the NAC region, C terminal region).