The cellular pathology of Parkinson's disease

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause that occurs in adults. The presence of Lewy bodies (LB) in association with nerve cell loss in the substantia nigra and various other regions of the nervous system is a diagnostic hallmark of the disease. In 1997, a mutation was identified in the alpha-synuclein gene in families with autosomal dominant PD. Subsequent immunohistochemical studies have revealed that all of the LB in familial and sporadic PD contain the gene product alpha-synuclein: abnormal filaments that constitute LB were clearly recognized by antibodies against alpha-synuclein. Moreover, it was shown that the glial cells, both astrocytes and oligodendrocytes, are also affected by alpha-synuclein pathology. Recently, a novel protein, synphilin-1, has been identified that interacts with alpha-synuclein. Interestingly, synphilin-1 immunohistochemistry has demonstrated that this protein is present in the central core of classical (brainstem) LB, which are composed mainly of densely packed vesicular structures. The role of both alpha-synuclein and synphilin-1 in normal conditions has yet to be clarified.