W Maruyama1 M Shamoto Nagai1 Y Akao2 P Riederer3 and M Naoi2

1 Department of Geriatric Medicine, National Institute for Geriatrics and Gerontology,

Obu, Aichi, and

2 Department of Neurosciences, Gifu International Institute for Biotechnology, Kakamigahara, Gifu, Japan 3 Clinical Neurochemistry and NPF Center of Excellence Laboratories, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

Summary. In Parkinson's disease (PD), the selective depletion of dopamine neurons in the substantia nigra, particular those containing neuromelanin (NM), is the characteristic pathological feature. The role of NM in the cell death of dopamine neurons has been considered either to be neurotoxic or neuroprotective, but the precise mechanism has never been elucidated. In human brain, NM is synthesized by polymerization of dopamine and relating quinones, to which bind heavy metals including iron. The effects of NM prepared from human brain were examined using human dopaminergic SH-SY5Y cells. It was found that NM inhibits 26S proteasome activity through generation of reactive oxygen and nitrogen species from mitochondria. The mi-tochondrial dysfunction was also induced by oxidative stress mediated by iron released from NM. NM accumulated in dopamine neurons in ageing may determine the selective vulnerability of dopamine neurons in PD.

Was this article helpful?

0 0
All About Alzheimers

All About Alzheimers

The comprehensive new ebook All About Alzheimers puts everything into perspective. Youll gain insight and awareness into the disease. Learn how to maintain the patients emotional health. Discover tactics you can use to deal with constant life changes. Find out how counselors can help, and when they should intervene. Learn safety precautions that can protect you, your family and your loved one. All About Alzheimers will truly empower you.

Get My Free Ebook

Post a comment