Linking the cerebellum to Parkinson disease: an update

Li, Tianbai; Le, Weidong; Jankovic, Joseph

doi:10.1038/s41582-023-00874-3

Cited by 14 publications

(5 citation statements)

References 132 publications

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“…Therefore, we map the localization of nonmotor and motor functional areas within the cerebellum (Figure 1). We find that the previous functional regions of the cerebellum can mainly divide into the “motor” cerebellum (comprising lobules V, VI, VIIb, and VIII) and the “cognitive” cerebellum (comprising Crus I and II) 122 . However, according to the existing research, the “motor” cerebellum and the “cognitive” cerebellum are not as distinct as previously mentioned but rather as a state of mutual integration (Figure 1).…”

Section: Cerebellum and Admentioning

confidence: 62%

“…The cerebellum has emerged as a new frontier for research in AD and other dementias. Cerebellar dysfunction is also becoming a prominent theme in other NDs, including PD, 122 ALS, HD, and SCA. In this review, we explore the role of the cerebellum in the pathogenesis of various NDs and highlight the cerebellar vulnerabilities that may contribute to the development of these disorders.…”

Section: Cerebellum and Other Ndsmentioning

confidence: 99%

“…There is growing recognition that cerebellar involvement may explain some of the motor and nonmotor symptoms associated with PD (Table 1). 122 Furthermore, studies have demonstrated pathophysiological and imaging changes in the cerebellum of PD patients 122 …”

Section: Cerebellum and Other Ndsmentioning

confidence: 99%

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Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

Yang,

Liu,

Chen

et al. 2024

MedComm

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The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non‐specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.

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Section: Cerebellum and Admentioning

confidence: 62%

Section: Cerebellum and Other Ndsmentioning

confidence: 99%

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Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

Yang,

Liu,

Chen

et al. 2024

MedComm

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“…The cerebellum was chosen as stimulation target, because of growing evidence for pathophysiological involvement of the cerebellum in PD. 28,29 New findings in anatomical connections linking the cerebellum and the basal ganglia support this hypothesis. 30 We stimulated 3 cerebellar sites, because this protocol was effective in patients with spinocerebellar ataxia (SCA) in previous studies.…”

Section: Methodsmentioning

confidence: 95%

RTMS of the Cerebellum Using an Accelerated Stimulation Protocol Improved Gait in Parkinson’s Disease

Grobe-Einsler,

Lupa,

Weller

et al. 2024

Neurorehabil Neural Repair

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Background Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological and noninvasive brain stimulation technique that has been proven to be effective in Parkinson’s disease (PD). The combination of rTMS and treadmill training improved gait function in PD greater than treadmill training alone. Objective The aim of our study was to evaluate the combination of a novel high-intensity, short intervention rTMS treatment and a multimodal treatment protocol including of physiotherapy, occupational therapy and language therapy, the so-called Parkinson’s Disease Multimodal Complex Treatment (PD-MCT), to improve motor function. Methods In this randomized double-blind sham-controlled trial rTMS with 48 Hz or sham was applied over the cerebellum 3 times a day for 5 consecutive days. Patients were assessed at baseline (V0), after 5 days of treatment (V1), and 4 weeks later (V2). The primary clinical outcome measure was the motor sum-score of the Unified PD Rating Scale (UPDRSIII), secondary clinical outcomes were quantitative motor tasks. Results A total of 36 PD patients were randomly allocated either to rTMS (n = 20) or sham (n = 16), both combined with PD-MCT. rTMS improved the UDPRSIII score comparing baseline and V1 in the treatment group by −8.2 points ( P = .004). The 8MW and dynamic posturography remained unchanged in both groups after intervention. Conclusion. Compressing weeks of canonical rTMS protocols into 5 days was effective and well tolerated. rTMS may serve as an add-on therapy for augmenting the multimodal complex treatment of motor symptoms, but seems to be ineffective to treat postural instability.

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“…For instance, in AD, the rst tissues degenerating are the parahippocampal gyrus and the olfactory bulb, followed by the degeneration of the hippocampus, leading to the characteristic clinical dementia symptoms [8][9][10][11] . PD in contrast, affects mostly the dopaminergic innervation of the mid brain and, according to more recent studies, also the cerebellum, resulting in the perturbation of motility and the induction of tremor syndromes 12,13 . Why and how distinct brain regions are differently affected in neurodegenerative diseases and whether different neuron classes would show intrinsically different aging trajectories is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Neuron-type specific aging-rate reveals age decelerating interventions preventing neurodegeneration

Schumacher,

Gallrein,

Meyer

2024

Preprint

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Different types of neurons show distinct susceptibility to age-dependent functional decline and degeneration and are linked to different types of neurodegenerative disorders. The underlying reasons for different aging trajectories of distinct neuron types are poorly understood. Here, we employ aging clocks to assess whether distinct neurons differ in their biological age trajectory in C. elegans where the identity of each single neuron is known. We find that specifically ciliated sensory neurons with high neuropeptide expression show the most rapidly progressing biological age. The more rapidly aging neurons show a reduction of mitochondrial respiration and elevated protein translation gene expression. Reducing protein translation with cycloheximide effectively protected fast aging neurons. We show that the C. elegans neuronal aging pattern are highly correlated with human brain aging and contrasted by geroprotective interventions. We performed an in silico drug screen and identified known and novel neuroprotective small molecule compounds. We show that the natural occurring plant metabolite syringic acid and the piperazine derivative vanoxerine delay neuronal degeneration and propose that they could serve as neuroprotective interventions. We also identify neurotoxins that accelerate neurodegeneration indicating that this approach could reveal interventions as well as risk factors for neuronal aging.

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Linking the cerebellum to Parkinson disease: an update

Cited by 14 publications

References 132 publications

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

RTMS of the Cerebellum Using an Accelerated Stimulation Protocol Improved Gait in Parkinson’s Disease

Neuron-type specific aging-rate reveals age decelerating interventions preventing neurodegeneration

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