Folding Underlies Bidirectional Role of GPR37/Pael-R in Parkinson Disease

Leinartaité, Lina; Svenningsson, Per

doi:10.1016/j.tips.2017.05.006

Cited by 28 publications

(26 citation statements)

References 105 publications

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“…(iv) GPR structure in idiopathic PD Lewy bodies. (Leinartaité & Svenningsson, 2017). viFurthermore, ex-vivo experiments show that α-synuclein can inhibit GCase activity at lysosomal pH.…”

Section: Background To Studymentioning

confidence: 99%

GBA RNAi but not catalytic inhibition of glucocerebrosidase with Conduritol-β-epoxide increases levels of total α-synuclein in SH-SY5Y cells

Zurbruegg

Chan

Svenningsson

2019

Neuroscience Letters

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“…(iv) GPR structure in idiopathic PD Lewy bodies. (Leinartaité & Svenningsson, 2017). viFurthermore, ex-vivo experiments show that α-synuclein can inhibit GCase activity at lysosomal pH.…”

Section: Background To Studymentioning

confidence: 99%

GBA RNAi but not catalytic inhibition of glucocerebrosidase with Conduritol-β-epoxide increases levels of total α-synuclein in SH-SY5Y cells

Zurbruegg

Chan

Svenningsson

2019

Neuroscience Letters

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“…Relevant to neurodegeneration, Parkin has been reported to interact with a glycosylated form of α-syn (a-Sp22) [ 80 ]; synphilin, an α-synuclein-interacting protein [ 81 ]; and synaptotagmin XI (SYT11), involved in regulation of the synaptic vesicle pool and release [ 82 , 83 , 84 ]. In addition, parkin ubiquitinates the parkin-associated endothelin-receptor-like receptor (Pael-R/GPR37) and promotes degradation of its insoluble form [ 85 ]. Pael-R/GPR37 interacts with the dopamine transporter (DAT, SLC6A3) and modulates DAT activity [ 86 ].…”

Section: Genes Linked To Neurodegenerative Diseases Also Play a Romentioning

confidence: 99%

The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

Torres

Wassouf

Zafar

et al. 2020

IJMS

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Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes, which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

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“…GPR37 is a glia-enriched oGPCR implicated in many neuropathologies, such as MDD, BPD, autism, and Parkinson’s disease [ 59 , 140 , 141 ]. Despite indications of GPR37 pairing with four peptides—head activator (HA) [ 142 ], prosaposin (PSAP) [ 143 ], bioactive lipid neuroprotectin D1 (NPD1) [ 144 ], and regenerating islet-derived family member 4 (Reg4) [ 145 ]—certain and reproducible proofs of receptor activation are still missing [ 146 ]. Recently, it has been proposed that a native cellular environment is a requirement to obtain proper GPR37 activation [ 147 ].…”

Section: Systematic Analysis Of Ogpcrs In Anxiety and Mood Disordementioning

confidence: 99%

Orphan G Protein Coupled Receptors in Affective Disorders

Watkins

Orlandi

2020

Genes

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G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B.

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Folding Underlies Bidirectional Role of GPR37/Pael-R in Parkinson Disease

Cited by 28 publications

References 105 publications

GBA RNAi but not catalytic inhibition of glucocerebrosidase with Conduritol-β-epoxide increases levels of total α-synuclein in SH-SY5Y cells

GBA RNAi but not catalytic inhibition of glucocerebrosidase with Conduritol-β-epoxide increases levels of total α-synuclein in SH-SY5Y cells

The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

Orphan G Protein Coupled Receptors in Affective Disorders

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