Chapter 2 - Synuclein misfolding as a therapeutic target

Abstract

Deposits of misfolded proteins are a key hallmark of many neurodegenerative disorders. They form proteinaceous inclusion bodies at specific predilection sites within the central nervous system and are characteristic for neurodegenerative protein misfolding diseases. Already in the beginning of 20th century, Friederich Lewy identified large inclusion bodies in the brain of a patient who was diagnosed with Parkinson’s disease. They were found inside neuronal cell bodies and axons, and were termed accordingly, Lewy bodies and Lewy neurites. Lewy described these inclusions or “Negrischen Körperchen” and compared them with lesions that are caused in the central nervous system after exposure to infectious viral pathogens. Although it was clear that these characteristic histopathological hallmarks had an important role in the disease process, the exact anatomical substrate of these large inclusions remained elusive and a search was set out to identify this pathognomonic component.