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PINK1, a gene product of PARK6, accumulates in α-synucleinopathy brains
  1. Tetsuro Murakami1,
  2. Yasuhiro Moriwaki2,
  3. Takeshi Kawarabayashi3,
  4. Makiko Nagai3,
  5. Yasuyuki Ohta3,
  6. Kentaro Deguchi3,
  7. Tomoko Kurata3,
  8. Nobutoshi Morimoto3,
  9. Yasushi Takehisa3,
  10. Etsuro Matsubara4,
  11. Masaki Ikeda5,
  12. Yasuo Harigaya6,
  13. Mikio Shoji7,
  14. Ryosuke Takahashi8,
  15. Koji Abe9
  1. 1Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  2. 2Kyoritsu University of Pharmacy, Department of Clinical Pharmacy, Division of Pharmacology, Tokyo, Japan
  3. 3Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  4. 4Department of Alzheimer’s Disease Research, National Institute of Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan
  5. 5Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan
  6. 6Department of Neurology, Maebashi Red Cross Hospital, Gunma, Japan
  7. 7Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan, and Department of Neurological Science, Institute of Brain Science, Hirosaki University School of Medicine, Aomori, Japan
  8. 8Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  9. 9Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  1. Correspondence to:
 Tetsuro Murakami
 Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan; neuron{at}cc.okayama-u.ac.jp

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α-Synucleinopathy is an entity of neurodegenerative diseases such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), that involves accumulation of α-synuclein in the brain. PINK1 (PTEN induced kinase 1) is a novel gene recently identified as causative in autosomal recessive early onset parkinsonism (PARK6). In the present study, we examined the localisation of PINK1 in the brains of patients with α-synucleinopathy and found PINK1 in glial cytoplasmic inclusions (GCIs) in MSA, as well as in Lewy bodies (LBs) in PD and DLB. These findings imply that PINK1 may be involved in the formation of LBs and GCIs, suggesting that PINK1 is one of the major pathological proteins in α-synucleinopathy.

Methods

The cDNA of PINK1, corresponding to 112–520 amino acids of the protein, was subcloned in a vector pET30(a) with a His tag. Anti-PINK1 antibody was generated against recombinant His tagged PINK1 by immunising a rabbit. The obtained antibody was affinity purified. A postmortem brain sample from a normal patient was homogenised, subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis and transferred to a membrane. After blocking in Tris buffered saline with 5% dry milk, the membrane was incubated with anti-PINK1 antibody (1:1000). The membrane was then incubated with a secondary antibody (1:2500; Amersham, Buckinghamshire, UK), and visualised with an enhanced chemiluminescent substrate (Pierce, Rockford, Illinois, USA). Immunohistochemical analysis was carried out with paraffin embedded midbrain sections from patients with sporadic PD, …

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