A review on pathology, mechanism, and therapy for cerebellum and tremor in Parkinson’s disease

Abstract

Tremor is one of the core symptoms of Parkinson’s disease (PD), but its mechanism is poorly understood. The cerebellum is a growing focus in PD-related researches and is reported to play an important role in tremor in PD. The cerebellum may participate in the modulation of tremor amplitude via cerebello-thalamo-cortical circuits. The cerebellar excitatory projections to the ventral intermediate nucleus of the thalamus may be enhanced due to PD-related changes, including dopaminergic/non-dopaminergic system abnormality, white matter damage, and deep nuclei impairment, which may contribute to dysregulation and resistance to levodopa of tremor. This review summarized the pathological, structural, and functional changes of the cerebellum in PD and discussed the role of the cerebellum in PD-related tremor, aiming to provide an overview of the cerebellum-related mechanism of tremor in PD.

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

“…Due to striatal dopamine deficiency, PD presents with dyskinesias, including impaired range and speed of movement, limb stiffness, or resting tremors. 218 Dopaminergic neurons in PD often exhibit Lewy bodies, in which there is massive accumulation of α-synuclein (αsyn) in the cytoplasm. 218 In PD patients, α-syn aggregation is widely regarded as a major causative factor.…”

“…218 Dopaminergic neurons in PD often exhibit Lewy bodies, in which there is massive accumulation of α-synuclein (αsyn) in the cytoplasm. 218 In PD patients, α-syn aggregation is widely regarded as a major causative factor. α-Syn oligomers form large, insoluble, neurotoxic fibrils called Lewy bodies.…”

Abnormal intra- and inter-network functional connectivity of brain networks in early-onset Parkinson’s disease and late-onset Parkinson’s disease

“…The cerebellum is involved in numerous functions (Stoodley and Schmahmann, 2010;Buckner, 2013;Steele et al, 2017), such as motor control, emotional processing, working memory. By means of PET-CT, fMRI and structural MRI, researchers have found that there are metabolic, functional as well as structural alterations in the cerebellum of PD patients and such alterations are associated with the production of motor and non-motor symptoms of PD (Wu and Hallett, 2013;Haghshomar et al, 2022;Zhong et al, 2022), especially tremor and cognitive impairment. A PET-based study revealed a tremor-related metabolic network in PD which showed increased activity of the cerebellum, primary motor cortex and caudate/putamen and correlated significantly and positively with clinical ratings of tremor.…”

Physiological Recordings of the Cerebellum in Movement Disorders

“…Alpha synuclein formed Lewy bodies have been found in the Bergmann glia and Purkinje cell axons in the cerebellum. Also, in PD patients, there is a presence of increased climbing fiber-Purkinje cell synapses as well as the presence of torpedoes in Purkinje cell axons demonstrating cerebellar involvement in PD [26,27].…”