Membrane Trafficking Illuminates a Path to Parkinson’s Disease
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- Hasegawa Takafumi
- Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine
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- Sugeno Naoto
- Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine
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- Kikuchi Akio
- Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine
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- Baba Toru
- Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine
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- Aoki Masashi
- Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine
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Abstract
<p>Parkinson’s disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself. Therefore, there is an urgent need for disease modification in terms of the delay or prevention of neurodegeneration. Recent advances in genetic and biochemical studies have provided unifying conceptual frameworks of the pathogenesis of PD. Particularly, membrane trafficking has aroused special attention as an initiator or enhancer of the neurodegenerative process that leads to PD. Defects in the cellular trafficking pathway result in synaptic dysfunction and the accumulation of misfolded α-synuclein. Likewise, changes in intracellular sorting and degradation profoundly influence the cellular trafficking of misfolded proteins, thereby facilitating the cell-to-cell spreading of hazardous α-synuclein species in a prion-like manner. Here, we will review our current knowledge of the functional roles of membrane trafficking in PD and will discuss how this cellular process could induce or facilitate the functional and pathological alterations in this disease.</p>
Journal
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 242 (1), 63-76, 2017
Tohoku University Medical Press