Synucleinopathies

Neurodegenerative disorders involving deposition of abnormal ALPHA-SYNUCLEIN in dopaminergic neurons and glial cells in the brain. Pathological aggregations of alpha-synuclein proteins results in LEWY BODIES and Lewy neurites; melanin granules in the SUBSTANTIA NIGRA and LOCUS COERULEUS; and glial cytoplasmic inclusions. Synucleinopathies are associated with mutation in the ALPHA-SYNUCLEIN (SNCA) gene on chromosome 4. PARKINSON DISEASE; LEWY BODY DISEASE with dementia; and MULTIPLE SYSTEM ATROPHY are prominent examples of synucleinopathy.

Also Known As:

Networked: 2123 relevant articles (56 outcomes, 229 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Parkinson Disease (Parkinson's Disease)
2.	Multiple System Atrophy
3.	Neuroinflammatory Diseases
4.	Synucleinopathies
5.	Tauopathies

Experts

1.	Masliah, Eliezer: 63 articles (01/2022 - 02/2002)
2.	Trojanowski, John Q: 52 articles (01/2022 - 05/2002)
3.	Lee, Virginia M-Y: 44 articles (11/2021 - 05/2002)
4.	Giasson, Benoit I: 42 articles (07/2022 - 05/2002)
5.	Rockenstein, Edward: 34 articles (01/2022 - 10/2004)
6.	Luk, Kelvin C: 31 articles (01/2022 - 11/2007)
7.	Hasegawa, Masato: 30 articles (01/2022 - 02/2002)
8.	Outeiro, Tiago F: 27 articles (01/2022 - 06/2012)
9.	Lee, Seung-Jae: 24 articles (02/2022 - 03/2010)
10.	Melki, Ronald: 24 articles (02/2022 - 03/2014)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Synucleinopathies:

1.	SynucleinsIBA 01/01/2018 - "α-synuclein high expresser mouse (α-Syn-tg; under mThy1 promoter, Line 61) was administrated with anti-TLR2 to examine that functional inhibition of TLR2 ameliorates neuropathology and behavioral defect in the synucleinopathy animal model. " 01/01/2018 - "These results indicate that targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable therapeutic strategy for treating diseases in which tau and α-synuclein have a synergistic toxicity." 01/01/2020 - "Collectively, our data provide a role of NK cells in modulating synuclein pathology and motor symptoms in a preclinical mouse model of PD, which could be developed into a therapeutic for PD and other synucleinopathies." 08/01/2013 - "The effects of ABL1/ABL inhibition on clearance of SNCA/α-synuclein were evaluated in animal models of α-synucleinopathies. " 01/01/2012 - "β-Synuclein (βS), the non-amyloidogenic homologue of αS, ameliorates the neurodegeneration phenotype of αS in transgenic (tg) mouse models, as well as in cell free and cell culture systems, which suggests that βS might be a negative regulator of neurodegeneration caused by αS, and that "loss of function" of βS might be involved in progression of α-synucleinopathies. "
2.	alpha-SynucleinIBA 01/01/2017 - "Surprisingly, inoculation of alpha-synuclein fibrils into the tongue was less effective in causing disease with only one of five injected animals showing alpha-synuclein pathology after 285 days. " 08/01/2011 - "Synphilin-1 inhibition of the proteasomal pathway of degradation of alpha-synuclein may help to understand the pathophysiological changes occurring in PD and other synucleinopathies." 01/01/2022 - "Alpha-synuclein Immunization Strategies for Synucleinopathies in Clinical Studies: A Biological Perspective." 01/01/2021 - "In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. " 01/01/2019 - "These studies provide novel evidence of USP13 effects on parkin and alpha-synuclein metabolism and suggest that USP13 is a potential therapeutic target in the alpha-synucleinopathies."
3.	Proteins (Proteins, Gene)FDA Link 01/01/2012 - "Evidence in transgenic models suggests a beneficial effect of microglial activity on clearance of proteins like Aβ and a detrimental effect on Tau modification, but the role of CX3CL1 signaling in α-synucleinopathies is less clear. " 10/01/2022 - "In the present study, by studying patients with PD (N = 8), DLB (N = 13), and MSA (N = 5) and controls (N = 16), we explored the involvement of Rubicon family proteins [Rubicon, Pacer and differentially expressed in FDCP8 (DEF8)] in synucleinopathies. " 06/01/2013 - "In this study, we examined the association between alpha-synucleinopathy and autophagy through immunohistochemical analysis of charged multivesicular body protein 2B (CHMP2B), a component of the ESCRT-pathway. " 07/28/2023 - "Collectively, these (and other) disorders are referred to as synucleinopathies, highlighting the relation between disease type and protein misfolding/aggregation. " 01/01/2023 - "Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. "
4.	Biomarkers (Surrogate Marker)IBA 01/01/2022 - "Computational modeling coupled with biomarkers of preclinical autonomic synucleinopathy may enable early detection and more effective treatment of LBDs." 11/17/2023 - "In Silico and In Vitro Study towards the Rational Design of 4,4'-Disarylbisthiazoles as a Selective α-Synucleinopathy Biomarker." 01/01/2023 - "In summary, the results of studies addressing the determinations of aSyn in its different forms in peripheral tissues (especially in platelets, skin, and digestive tract, but also salivary glands and olfactory mucosa), in combination with other potential biomarkers, could be a useful tool to discriminate PD from controls and from other causes of parkinsonisms, including synucleinopathies." 01/01/2023 - "Our study in IRBD shows that (1) RT-QuIC detects AS in the skin and CSF with similar high sensitivity, specificity, and agreement, (2) AS RT-QuIC positivity is associated with supportive features and biomarkers of synucleinopathy, and (3) skin punch biopsy and lumbar puncture have comparable mild adverse effects, tolerance, and acceptance. " 01/01/2023 - "The aim of this study was to determine the ability of three different biomarkers, including [18F]RO948 PET, to distinguish PSP patients from healthy controls and from patients with α-synucleinopathies. "
5.	Dopamine Plasma Membrane Transport Proteins (Dopamine Transporter)IBA 01/01/2021 - "Neuroimaging studies of striatal dopamine transporter uptake tracer signaling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early caudate dysfunction. " 01/01/2023 - "Second, we studied the association between 18F-fluorodeoxyglucose PET and lower dopamine transporter availability in the putamen, another hallmark of synucleinopathies. " 11/01/2010 - "Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]." 10/29/2019 - "The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. " 01/01/2021 - "Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder."
6.	VaccinesIBA 09/13/2023 - "The results from this study establish a fast and effective method to obtain rLTB-Syn, making it useful in the design of novel vaccine formulations targeting synucleinopathies." 11/30/2020 - "This study investigates the target specificity of three different active vaccines for pathological α-Syn aggregates found in human brain tissue from synucleinopathies. " 02/10/2020 - "Using carrot cells as biofactories and oral delivery vehicles of LTB-Syn: A low-cost vaccine candidate against synucleinopathies." 06/01/2017 - "LTB-Syn: a recombinant immunogen for the development of plant-made vaccines against synucleinopathies." 01/01/2023 - "Evaluation of an Adoptive Cellular Therapy-Based Vaccine in a Transgenic Mouse Model of α-synucleinopathy."
7.	Toll-Like Receptor 2IBA 10/31/2019 - "In this review, we consolidate our key findings and recent studies concerning the role of Toll-like receptor 2 (TLR2), a pattern recognition innate immune receptor, in the pathogenesis of synucleinopathies. " 10/31/2019 - "Targeting Microglial and Neuronal Toll-like Receptor 2 in Synucleinopathies." 01/01/2018 - "Toll-Like Receptor 2 Signaling and Current Approaches for Therapeutic Modulation in Synucleinopathies." 10/27/2015 - "Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy." 01/01/2021 - "Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). "
8.	Caffeine (No Doz)FDA LinkGeneric 12/18/2018 - "Considering epidemiologic and experimental evidence suggesting protective effects of caffeine in PD, we sought, in the present study, to test whether there is synergy between EHT and caffeine in models of α-synucleinopathy. " 01/01/2018 - "We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. " 01/01/2018 - "Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum." 01/01/2022 - "We describe prototypical, relatively low-risk drug candidates for such trials (e.g., albuterol, ambroxol, caffeine, ibuprofen), tailored to specific at-risk populations ranging from pathogenic LRRK2 or GBA gene variant carriers to those defined by prodromal PD and α-synucleinopathy. "
9.	Peptides (Polypeptides)IBA 12/01/2017 - "Recent studies using synthetic αS peptides, a cell culture model, transgenic mice models, and human samples such as cerebrospinal fluids and the blood of PD patients have suggested that pre-fibrillar forms of αS (i.e., oligomers) are more critical than fibrillar forms (such as Lewy bodies) in the pathogenesis of α-synucleinopathies. " 01/01/2023 - "Our findings suggest that the αSyn decoy peptide represents a novel therapeutic approach for reducing the accumulation of toxic αSyn-FABP3 oligomers in the brain, thereby preventing the progression of synucleinopathies." 06/19/2022 - "Our results demonstrate that it is possible to regulate αSyn-VDAC complexation by a rationally designed peptide, thus suggesting new avenues in the search for peptide therapeutics to alleviate αSyn mitochondrial toxicity in PD and other synucleinopathies." 03/19/2015 - "In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation. " 02/01/2016 - "Misfolding and aggregation of this normally soluble, 140-residue polypeptide underlies a group of neurodegenerative disorders called synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). "
10.	Neurotransmitter Agents (Neurotransmitter)IBA 12/01/2020 - "While the involvement of multiple neurotransmitter systems in α-synucleinopathies is reported, a comprehensive study on their metabolic connectivity reconfiguration in the preclinical and clinical disease-spectrum is lacking. " 01/01/2017 - "Since many neurotransmitter systems utilize these receptor signaling pathways to mediate different abilities affected in Parkinson's disease, we argue this novel perspective might be helpful in designing treatment strategies for some of the non-motor symptoms in Parkinson's disease and synucleinopathies." 11/01/2021 - "We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with α-synucleinopathy (385 PD patients and 67 DLB patients). " 06/01/2010 - "The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. " 06/01/2019 - "Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. "

Therapies and Procedures

1.	Therapeutics 09/15/2023 - "The hGCase immunofluorescence, immunoprecipitation, and AlphaLISA assays utilizing hGCase-1/17 and hGCase-1/23 will not only facilitate improved investigations of hGCase biology, but can also serve as tools to assess the distribution and effectiveness of GCase-targeted therapies for PD and related synucleinopathies." 01/01/2023 - "The iPSC lines could facilitate disease-modelling and therapy development studies for synucleinopathies." 01/01/2023 - "Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics." 04/25/2022 - "Our study sheds new light into the enhanced vulnerability of the midbrain in PD-related synaptic dysfunction and suggests that glycation suppressors and anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies." 01/01/2022 - "Such findings would greatly deepen our understanding of synucleinopathies and the potential link between strain and phenotypic variability, which may enable specific diagnosis of different synucleinopathies in the prodromal phase, creating a large therapeutic window with potential future applications in clinical trials and personalized therapeutics."
2.	Immunotherapy 01/01/2018 - "In summary, the study provides evidence for the biological efficacy of immunotherapy in a transgenic mouse model of oligodendroglial synucleinopathy. " 01/01/2018 - "This study proposes TLR2 immunotherapy as a novel therapeutic strategy for synucleinopathies of the aging population." 01/01/2017 - "Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of α-syn. " 01/01/2020 - "Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities." 01/01/2020 - "Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. "
3.	Precision Medicine 01/01/2016 - "This forthcoming knowledge will support the development of precision medicine for synucleinopathies." 08/25/2023 - "Elucidating the molecular underpinnings of heterogeneity amongst α-synucleinopathies holds promise for future clinical translation, allowing for the development of personalized medicine approaches tackling the root cause of each α-synucleinopathy." 01/01/2019 - "Glucocerebrosidase mutations and synucleinopathies: Toward a model of precision medicine."
4.	Deep Brain Stimulation 01/01/2021 - "Further, STN DBS has the potential to exert protective effects by modifying the long-term neurodegenerative consequences of synucleinopathy.SIGNIFICANCE STATEMENT An increase in brain-derived neurotrophic factor (BDNF) has been linked to the neuroprotection elicited by subthalamic nucleus (STN) deep brain stimulation (DBS) in neurotoxicant models of Parkinson's disease (PD). "
5.	Denervation 08/01/2009 - "In this study we assessed olfactory function in PAF in comparison with the two other synucleinopathies and whether olfactory dysfunction correlates with neuroimaging evidence of cardiac noradrenergic or nigrostriatal dopaminergic denervation. " 11/01/2018 - "PD and AP with possible alpha-synucleinopathies share the features of marked cervical denervation and the presence of 5G4. " 01/01/2013 - "Cardiac sympathetic neuroimaging and postmortem neuropathological findings have linked α-synucleinopathy with noradrenergic denervation in Lewy body diseases. " 02/01/2012 - "Sympathetic noradrenergic before striatal dopaminergic denervation: relevance to Braak staging of synucleinopathy." 06/01/2012 - "This review updates the field of autonomic cardiovascular abnormalities in PD and related disorders, with emphasis on relationships among striatal dopamine depletion, sympathetic noradrenergic denervation, and alpha-synucleinopathy."