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

TY - JOUR

T1 - Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease

AU - Hindle, Samantha J

AU - Elliott, Christopher J H

PY - 2013/3/25

Y1 - 2013/3/25

N2 - 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.

AB - 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.

U2 - 10.4161/auto.24397

DO - 10.4161/auto.24397

M3 - Article

C2 - 23529190

SN - 1554-8627

VL - 9

SP - 936

EP - 938

JO - Autophagy

JF - Autophagy

IS - 6

ER -