Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease.

Abstract:

:Flies expressing the most common Parkinson disease (PD)-related mutation, LRRK2-G2019S, in their dopaminergic neurons show loss of visual function and degeneration of the retina, including mitochondrial abnormalities, apoptosis and autophagy. Since the photoreceptors that degenerate are not dopaminergic, this demonstrates nonautonomous degeneration, and a spread of pathology. This provides a model consistent with Braak's hypothesis on progressive PD. The loss of visual function is specific for the G2019S mutation, implying the cause is its increased kinase activity, and is enhanced by increased neuronal activity. These data suggest novel explanations for the variability in animal models of PD. The specificity of visual loss to G2019S, coupled with the differences in neural firing rate, provide an explanation for the variability between people with PD in visual tests.

journal_name

Autophagy

journal_title

Autophagy

authors

Hindle SJ,Elliott CJ

doi

10.4161/auto.24397

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

936-8

issue

6

eissn

1554-8627

issn

1554-8635

pii

24397

journal_volume

9

pub_type

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