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JCI online early table of contents: Jan. 2, 2008
Date:1/2/2008

lpha-synuclein by processes such as by phosphorylation and nitration was shown to impair degradation of this protein by a mechanism known as chaperone-mediated autophagy (CMA) in isolated lysosomes, cultured dopaminergic cell lines, and cultured mouse neurons. Of relevance to PD, in which most of the neurons lost are dopaminergic neurons of the substantia nigra, dopamine-modified alpha-synuclein was poorly degraded by CMA and blocked the degradation of other proteins by CMA. The authors therefore suggested that dopamine-induced inhibition of alpha-synuclein degradation by CMA increases the vulnerability of dopaminergic neurons to cellular stressors, thereby explaining the selective loss of dopaminergic neurons in individuals with PD.

TITLE: Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy

AUTHOR CONTACT:
Ana Maria Cuervo
Albert Einstein College of Medicine of Yeshiva University, New York, New York, USA.
Phone: (718) 430-2689; Fax: (718) 430-8975; E-mail: amcuervo@aecom.yu.edu.

MEDIA CONTACT:
Karen Gardner
Media Relations Manager
Albert Einstein College of Medicine of Yeshiva University, New York, New York, USA.
Phone: (718) 430-3101; E-mail: kgardner@aecom.yu.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=32806


NEUROBIOLOGY

Lidocaine can really get on your nerves: Local anesthetics interact with the ion channel TRVP1 on neurons

Very high concentrations of local anesthetics (LAs), such as lidocaine, are often used clinically for spinal anesthesia and for peripheral region anesthesia. Although neuronal damage and death (neurotoxicity) are well-documented potential side effects of these extreme doses of LAs, the mechanism(s) underlying the neurotoxicity has
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Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
Source:Eurekalert

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