Widespread expression of a-synuclein in neuronal cytoplasm and glial cells in the central and peripheral nervous systems in human

摘要

a-Synuclein (aS), a presynaptic nerve terminal protein, is now known to be a major component of neuronal and glial cytoplasmic inclusions in Lewy body (LB) disease and multiple system atrophy (MSA). However, aS has not been identified in either neuronal or glial cytoplasm in normal conditions. Recently, we demonstrated that aS was recognized by immunostaining in the cytoplasm of neurons, astrocytes and oligodendrocytes in vibratome sections, but not paraffin sections, from the normal human brain. Pretreatment with proteinase K and formic acid increased the intensity of aS immunoreactivity in these cells. The distribution of aS-immunoreactive neurons appears to be similar to that of intraneuronal inclusions in the brain of a-synuclein transgenic mice and the predilection sites for Lewy bodies. Moreover, aS was normally expressed in the cytoplasm of neurons and Schwann cells in the peripheral nervous system. These findings suggest that a significant amount of aS is also present in the neuronal and glial cytoplasm in the central and peripheral nervous systems. It is possible that specific upregulation and/or insufficient degradation of aS may contribute to inclusion body formation. ?2003 Elsevier Science B.V. All rights reserved.