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Parkinson’s disease: how should we consider the selectivity and progressivity of its neuropathology? |
| Wei Li1, Xiaohan Yu1, Shun Yu1,2,3,4* |
| 1. Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
2. Clinical Center for Parkinson’s Disease, Capital Medical University, Beijing 100053, China
3. Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson’s Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing 100053, China
4. National Clinical Research Center for Geriatric Disorders, Beijing 100053, China |
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Abstract Parkinson’s disease (PD) is a common age-related neurodegenerative disease characterized by movement disorders. The hallmark pathological lesions of PD are the formation of Lewy pathology in selected populations of neurons throughout the nervous system. Braak and his colleagues created a staging system for PD describing the connection between Lewy pathology and disease severity. They proposed that Lewy pathology might be initially triggered by exogenous pathogens targeting the enteric or olfactory nervous system, then spread in a prion-like propagation manner from the peripheral nerves to the lower brainstem and midbrain, before finally reaching higher cortical structures, causing a sequential occurrence of the non-motor and motor symptoms, depending on the lesioned neurons. However, emerging evidence also supports a functional threshold hypothesis proposed by Engelender and Isacson in which Lewy pathology may occur parallelly in the central and peripheral nervous systems and the symptoms only begin when the functional reserve of the affected neurons (and their connecting brain regions) is unable to allow for network compensation. Consequently, early symptoms of PD reflect the loss of function in the least compensated systems, such as the enteric and olfactory nervous systems, rather than the spread of Lewy pathology from the peripheral to the central nervous systems. The current review article provides a comprehensive overview of the evidence supporting a merged mechanism that the neurodegeneration in PD happens to those neurons that are not only intrinsically vulnerable but also affected by the spread of Lewy pathology.
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| Keywords
Parkinson’s disease (PD)
Lewy body(LB)
α-synuclein (α-syn) motor symptom
non-motor symptom
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Issue Date: 23 March 2020
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