Thoracic trauma promotes alpha-Synuclein oligomerization in murine Parkinson's disease

Ruf, Wolfgang; Palmer, Annette; Dörfer, Lena; Wiesner, Diana; Buck, Eva; Grozdanov, Veselin; Kassubek, Jan; Dimou, Leda; Ludolph, Albert C.; Huber‐Lang, Markus; Danzer, Karin M

doi:10.1016/j.nbd.2022.105877

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…Literature on the potential pathogenesis of PIMD other than dystonia is scarce, probably due to the rarity of such conditions. A recently published study explored the possibility that thoracic trauma could trigger central pathological changes in mouse models of PD [161]. The findings from this study provided evidence that peripheral injury (i.e., blunt thoracic trauma) results in an increased inflammatory response and alpha synuclein oligomerization in the brains of transgenic mice overexpressing alpha synuclein and behavioral features of parkinsonism.…”

Section: Possible Pathophysiologic Mechanismsmentioning

confidence: 81%

“…There was a clear increase in alpha synuclein oligomers in PD mice exposed to thoracic trauma compared to sham-treated mice. The authors suggested that "peripheral injury influences protein aggregation in the brain of PD mice" and hypothesized that "here could be an immediate ascending inflammatory reaction from the periphery that eventually reaches the CNS" [161]. While this study did not explicitly demonstrate a causal relationship between peripheral trauma and de novo parkinsonism, it supports the "twohit" hypothesis, i.e., in predisposed individuals (first hit), trauma (second hit) results in increased alpha synuclein oligomerization.…”

Section: Possible Pathophysiologic Mechanismsmentioning

confidence: 99%

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Peripherally-induced Movement Disorders: An Update

Lenka¹,

Jankovic

2023

Tremor and Other Hyperkinetic Movements

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Background: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.Methods: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 to identify relevant articles for this narrative review. Results:The spectrum of the phenomenology of PIMD is broad and it encompasses both hyperkinetic and hypokinetic movements. Hemifacial spasm is probably the most common PIMD. Others include dystonia, tremor, parkinsonism, myoclonus, painful leg moving toe syndrome, tics, polyminimyoclonus, and amputation stump dyskinesia. We also highlight conditions such as neuropathic tremor, pseudoathetosis, and MYBPC1associated myogenic tremor as examples of PIMD.Discussion: There is considerable heterogeneity among PIMD in terms of severity and nature of injury, natural course, association with pain, and response to treatment. As some patients may have co-existing functional movement disorder, neurologists should be able to differentiate the two disorders. While the exact pathophysiology remains elusive, aberrant central sensitization after peripheral stimuli and maladaptive plasticity in the sensorimotor cortex, on a background of genetic (two-hit hypothesis) or other predisposition, seem to play a role in the pathogenesis of PIMD.

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Section: Possible Pathophysiologic Mechanismsmentioning

confidence: 81%

Section: Possible Pathophysiologic Mechanismsmentioning

confidence: 99%

Peripherally-induced Movement Disorders: An Update

Lenka¹,

Jankovic

2023

Tremor and Other Hyperkinetic Movements

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α-Synuclein pathology from the body to the brain: so many seeds so close to the central soil

Yang,

Zhang

2023

Neural Regeneration Research

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α-Synuclein is a protein that mainly exists in the presynaptic terminals. Abnormal folding and accumulation of α-synuclein are found in several neurodegenerative diseases, including Parkinson's disease. Aggregated and highly phosphorylated α-synuclein constitutes the main component of Lewy bodies in the brain, the pathological hallmark of Parkinson's disease. For decades, much attention has been focused on the accumulation of α-synuclein in the brain parenchyma rather than considering Parkinson's disease as a systemic disease. Recent evidence demonstrates that, at least in some patients, the initial α-synuclein pathology originates in the peripheral organs and spreads to the brain. Injection of α-synuclein preformed fibrils into the gastrointestinal tract triggers the gut-to-brain propagation of α-synuclein pathology. However, whether α-synuclein pathology can occur spontaneously in peripheral organs independent of exogenous α-synuclein preformed fibrils or pathological α-synuclein leakage from the central nervous system remains under investigation. In this review, we aimed to summarize the role of peripheral α-synuclein pathology in the pathogenesis of Parkinson's disease. We also discuss the pathways by which α-synuclein pathology spreads from the body to the brain.

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Thoracic trauma promotes alpha-Synuclein oligomerization in murine Parkinson's disease

Cited by 2 publications

References 33 publications

Peripherally-induced Movement Disorders: An Update

Peripherally-induced Movement Disorders: An Update

α-Synuclein pathology from the body to the brain: so many seeds so close to the central soil

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