Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies
2002; American Society for Clinical Investigation; Volume: 110; Issue: 10 Linguagem: Inglês
10.1172/jci15777
ISSN1558-8238
AutoresManuela Neumann, Philipp J. Kahle, Benoit I. Giasson, Laurence Ozmen, Edilio Borroni, Will Spooren, Veronika Müller, Sabine Odoy, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, John Q. Trojanowski, Hans A. Kretzschmar, Christian Haass,
Tópico(s)Nerve injury and regeneration
ResumoThe 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.
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