[HTML][HTML] Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies

M Neumann, PJ Kahle, BI Giasson… - The Journal of …, 2002 - Am Soc Clin Investig
M Neumann, PJ Kahle, BI Giasson, L Ozmen, E Borroni, W Spooren, V Müller, S Odoy…
The Journal of clinical investigation, 2002Am Soc Clin Investig
The pathological modifications of α-synuclein (αS) in Parkinson disease and related
diseases are poorly understood. We have detected misfolded αS in situ based on the
proteinase K resistance (PK resistance) of αS fibrils, and using specific antibodies against
S129-phosphorylated αS as well as oxidized αS. Unexpectedly massive neuritic pathology
was found in affected human brain regions, in addition to classical αS pathology. PK
resistance and abnormal phosphorylation of αS developed with increasing age in (Thy1)-h …
The pathological modifications of α-synuclein (αS) in Parkinson disease and related diseases are poorly understood. We have detected misfolded αS in situ based on the proteinase K resistance (PK resistance) of αS fibrils, and using specific antibodies against S129-phosphorylated αS as well as oxidized αS. Unexpectedly massive neuritic pathology was found in affected human brain regions, in addition to classical αS pathology. PK resistance and abnormal phosphorylation of αS developed with increasing age in (Thy1)-h[A30P] αS transgenic mice, concomitant with formation of argyrophilic, thioflavin S-positive, and electron-dense inclusions that were occasionally ubiquitinated. αS pathology in the transgenic mice was predominantly in the brainstem and spinal cord. Astrogliosis was found in these heavily affected tissues. Homozygous mice showed the same pathology approximately one year earlier. The transgenic mice showed a progressive deterioration of locomotor function.
The Journal of Clinical Investigation