Anti-DARPP32 antibody-immunopositive inclusions in the brain of patients with multiple system atrophy.
MSA is a neurodegenerative disease and GCIs are specific pathological hallmarks in the brain of MSA patients. Recently, Cdk5 immunopositive GCIs were reported, but the function of Cdk5 in the adult human brain is not clear. Cdk5 has several substrates such as neurofilament and tau proteins. Among these substrates, tau and MAP 1B are immunopositive in GCIs. DARPP32 has been identified as a target for dopamine and PKA in the striatum. DARPP32 has multiple phosphorylation sites, and Cdk5 can phosphorylate DARPP32 at Thr75. The phosphorylation ofThr75 converts DARPP32 into an inhibitor of PKA. DARPP32 is also one of the major substrates of Cdk5, and DARPP32 is widely expressed in both neurons and glial cells. In this study, we determined the immunohistochemical localization of DARPP32 in the brains of a normal control group and patients with MSA. An anti-DARPP32 antibody revealed immunopositive oligodendrocytes and astrocytes widely distributed in the brains of the normal control group and the brain of patients with MSA. Neurons in the caudate, globus pallidus, substantia nigra, hypothalamus, neocortex layers II and III, and cerebellar Purkinje cells were all immunopositive for DARPP32 in the normal control brains, and the immunostaining patterns were very similar to those observed in patients with MSA. We found that DARPP32 was immunopositive in GCIs, and the localization of DARPP32 and Cdk5 was very similar in GCIs. We suggest that Cdk5 and its substrate DARPP32 may be involved in the formation of GCIs through the phosphorylation of DARPP32 in the oligodendrocytes of brains with MSA.
Honjo
Y
Y
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan. honjyo@kuhp.kyoto-u.ac.jp
Shirakashi
Y
Y
Kawamoto
Y
Y
Akiguchi
I
I
D000368:Aged; D000906:Antibodies; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology
D000906:Antibodies; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human