Neuroinflammatory Responses and Parkinson’ Disease: Pathogenic Mechanisms and Therapeutic Targets

Li, Yang; Mao, Kanming; Yu, Honglin; Chen, Jialong

doi:10.1007/s11481-020-09926-7

Cited by 51 publications

(39 citation statements)

References 88 publications

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“…The immune system for instance gains increasing interest in PD research [17]. The death of dopaminergic neurons is accompanied by astrocytic dysfunction, microglia hyper-activation and activation of various inflammatory networks in the substantia nigra of PD [17]. Since the role of neuroinflamma-tion is increasingly recognized in PD [18,19], potentially new therapeutics may target neuroinflammatory processes in PD [20].…”

Section: Discussionmentioning

confidence: 99%

Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review

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Brüggemann

Lohmann

2021

JND

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Parkinson’s disease (PD) is a disabling neurological condition characterized by the loss of dopaminergic neurons. Currently, the treatment for PD is symptomatic and compensates for the endogenous loss of dopamine production. In cases where the pharmacological therapy is only partly beneficial or results in major wearing-off complications, surgical interventions such as deep brain stimulation may be an alternative treatment. The disease cause often remains unknown, but in some patients, a monogenic cause can be identified. Mutations in at least six genes, LRRK2, SNCA, and VPS35 (dominant forms) or Parkin/PRKN, PINK1, and DJ1/PARK7 (recessive forms) have been unequivocally linked to PD pathogenesis. We here systematically screened 8,576 publications on these monogenic PD forms. We identified 2,226 mutation carriers from 456 papers. Levodopa was the most widely applied treatment; only 34 patients were indicated to be untreated at the time of reporting. Notably, detailed treatment data was rarely mentioned including response quantification (good, moderate, minimal) in 951 and/or dose in 293 patients only. Based on available data, levodopa showed an overall good outcome, especially in LRRK2, VPS35, Parkin, and PINK1 mutation carriers (“good” response in 94.6–100%). Side effects of levodopa therapy were reported in ∼15–40%of levodopa-treated patients across genes with dyskinesias as the most frequent one. Non-levodopa medication was indicated to be administered to <200 patients with mainly good outcome. Only a few reports were available on outcomes of brain surgery. Here, most mutation carriers showed a good response. Importantly, none of the available treatments is harmful to one genetic form but effective in another one. In the light of different medication schemes, the progressive nature of PD, and side effects, an improvement of therapeutic options for PD is warranted including a treatabolome database to guide clinicians in treatment decisions. Further, novel disease-cause-modifying drugs are needed.

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Section: Discussionmentioning

confidence: 99%

Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review

Over

Brüggemann

Lohmann

2021

JND

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“…PD is the second most common neurodegenerative disease [ 14 ]. It is characterized by intracellular inclusions containing α-syn aggregates forming the Lewy bodies (LB).…”

Section: Introductionmentioning

confidence: 99%

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Sastre

Montoro

Gálvez‐Martín

et al. 2020

IJMS

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Small guanosine triphosphatases (GTPases) of the Ras superfamily are key regulators of many key cellular events such as proliferation, differentiation, cell cycle regulation, migration, or apoptosis. To control these biological responses, GTPases activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and in some small GTPases also guanine nucleotide dissociation inhibitors (GDIs). Moreover, small GTPases transduce signals by their downstream effector molecules. Many studies demonstrate that small GTPases of the Ras family are involved in neurodegeneration processes. Here, in this review, we focus on the signaling pathways controlled by these small protein superfamilies that culminate in neurodegenerative pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Specifically, we concentrate on the two most studied families of the Ras superfamily: the Ras and Rho families. We summarize the latest findings of small GTPases of the Ras and Rho families in neurodegeneration in order to highlight these small proteins as potential therapeutic targets capable of slowing down different neurodegenerative diseases.

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“…Regarding PD, it is the second most common neurodegenerative disease. It is characterized by the accumulation of Lewy bodies, formed by α-synuclein (α-syn) aggregation, and by the selective degeneration of dopaminergic neurons of the substantia nigra pars compacta [ 14 ]. This results in disabilities in movements, including resting tremor and muscular rigidity.…”

Section: Introductionmentioning

confidence: 99%

“…This results in disabilities in movements, including resting tremor and muscular rigidity. Mutations in α-syn, in PTEN-induced putative kinase 1 (PINK1) and in leucine-rich repeat kinase 2 (LRRK2) have been associated with the risk of developing PD [ 14 ]. Apart from these mutations, mutations in the Rab39B GTPase have been related to the development of this disease [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

Sastre

Montoro

Lacerda

et al. 2021

IJMS

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Small guanosine triphosphatases (GTPases) of the Rab and Arf families are key regulators of vesicle formation and membrane trafficking. Membrane transport plays an important role in the central nervous system. In this regard, neurons require a constant flow of membranes for the correct distribution of receptors, for the precise composition of proteins and organelles in dendrites and axons, for the continuous exocytosis/endocytosis of synaptic vesicles and for the elimination of dysfunctional proteins. Thus, it is not surprising that Rab and Arf GTPases have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Both pathologies share characteristics such as the presence of protein aggregates and/or the fragmentation of the Golgi apparatus, hallmarks that have been related to both Rab and Arf GTPases functions. Despite their relationship with neurodegenerative disorders, very few studies have focused on the role of these GTPases in the pathogenesis of neurodegeneration. In this review, we summarize their importance in the onset and progression of Alzheimer’s and Parkinson’s diseases, as well as their emergence as potential therapeutical targets for neurodegeneration.

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Neuroinflammatory Responses and Parkinson’ Disease: Pathogenic Mechanisms and Therapeutic Targets

Cited by 51 publications

References 88 publications

Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review

Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review

Small GTPases of the Ras and Rho Families Switch on/off Signaling Pathways in Neurodegenerative Diseases

Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration

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