Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

Jolivalt, Corinne G.; Vu, Yvonne; Mizisin, Leah M.; Mizisin, Andrew P.; Calcutt, Nigel A.

doi:10.1097/nen.0b013e31817e23f4

Cited by 23 publications

(12 citation statements)

References 35 publications

(62 reference statements)

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“…If future studies support this model, then GPR37 and GPR37L1 may eventually serve as outstanding targets for novel therapeutics aimed at enhancing neuronal and glial survival in response to injury. Prosaposin and prosaptide have been shown to protect dopaminergic neurons in animal models of Parkinson disease (38,41), facilitate neuronal survival following focal cerebral ischemia (22,32), reduce neuropathic pain (37,40,57), and promote remyelination of nerves following injury (26,28,59). Thus, if future work in vivo upholds the idea that the neuroprotective and glioprotective actions of prosaposin and prosaptide are mediated by GPR37 and GPR37L1, the development of small molecule ligands for these receptors may provide new therapeutic possibilities for the treatment of Parkinson disease, stroke, neuropathic pain, and myelination disorders.…”

Section: Discussionmentioning

confidence: 99%

GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin

Meyer

Giddens

Schaefer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

175

237

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GPR37 (also known as Pael-R) and GPR37L1 are orphan G protein-coupled receptors that are almost exclusively expressed in the nervous system. We screened these receptors for potential activation by various orphan neuropeptides, and these screens yielded a single positive hit: prosaptide, which promoted the endocytosis of GPR37 and GPR37L1, bound to both receptors and activated signaling in a GPR37- and GPR37L1-dependent manner. Prosaptide stimulation of cells transfected with GPR37 or GPR37L1 induced the phosphorylation of ERK in a pertussis toxin-sensitive manner, stimulated 35 S-GTPγS binding, and promoted the inhibition of forskolin-stimulated cAMP production. Because prosaptide is the active fragment of the secreted neuroprotective and glioprotective factor prosaposin (also known as sulfated glycoprotein-1), we purified full-length prosaposin and found that it also stimulated GPR37 and GPR37L1 signaling. Moreover, both prosaptide and prosaposin were found to protect primary astrocytes against oxidative stress, with these protective effects being attenuated by siRNA-mediated knockdown of endogenous astrocytic GPR37 or GPR37L1. These data reveal that GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin.

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Section: Discussionmentioning

confidence: 99%

GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin

Meyer

Giddens

Schaefer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

175

237

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“…Injections of prosaptide TX14(A) were found to shorten recovery time from sciatic nerve crush as well as alleviate thermal hypoalgesia and formalin-evoked hyperalgesia in diabetic rats (Jolivalt et al, 2008b). Prosaptide TX14(A) was also able to enhance nerve regeneration distance and axonal diameter of the regenerated axons following sciatic nerve injury (Jolivalt et al, 2008b).…”

Section: Effects Of Secreted Prosaposin In the Nervous Systemmentioning

confidence: 99%

“…Prosaptide TX14(A) was also able to enhance nerve regeneration distance and axonal diameter of the regenerated axons following sciatic nerve injury (Jolivalt et al, 2008b). Prosaposin applied via a collagen-filled nerve guide after sciatic nerve transection in a guinea pig model increased the number of regenerating nerves, for both motor and sensory nerve types (Kotani et al, 1996a).…”

Section: Effects Of Secreted Prosaposin In the Nervous Systemmentioning

confidence: 99%

The protective role of prosaposin and its receptors in the nervous system

et al. 2014

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Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects. Following secretion, prosaposin can undergo endocytosis via an interaction with the low-density lipoprotein-related receptor 1 (LRP1). The ability of secreted prosaposin to promote protective effects in the nervous system is known to involve activation of G proteins, and the orphan G protein-coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling induced by both prosaposin and a fragment of prosaposin known as prosaptide. In this review, we describe recent advances in our understanding of prosaposin, its receptors and their importance in the nervous system.

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“…; impaired neurotrophic support 100 ; and increase in the inhibitory neurotransmitter GABA and depletion of spinal potassium-chloride cotransporters. 101 Correspondingly, diabetes-associated formalin-induced hyperalgesia was suppressed by several AR 99,102 and PARP 12,44 inhibitors, prosaposin-derived peptide, 100 and the GABA A receptor antagonist bicuculline 101 as well as insulin, 103 gabapentin, 104 and a B 1 , B 6 , and B 12 vitamin cocktail.…”

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confidence: 99%

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

2009

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Summary:Advanced peripheral diabetic neuropathy (PDN) is associated with elevated vibration and thermal perception thresholds that progress to sensory loss and degeneration of all fiber types in peripheral nerve. A considerable proportion of diabetic patients also describe abnormal sensations such as paresthesias, allodynia, hyperalgesia, and spontaneous pain. One or several manifestations of abnormal sensation and pain are described in all the diabetic rat and mouse models studied so far (i.e., streptozotocin-diabetic rats and mice, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats, Zucker diabetic fatty rats, and nonobese diabetic, Akita, leptin-and leptin-receptor-deficient, and highfat diet-fed mice). Such manifestations are 1) thermal hyperalgesia, an equivalent of a clinical phenomenon described in early PDN; 2) thermal hypoalgesia, typically present in advanced PDN; 3) mechanical hyperalgesia, an equivalent of pain on pressure in early PDN; 4) mechanical hypoalgesia, an equivalent to the loss of sensitivity to mechanical noxious stimuli in advanced PDN; 5) tactile allodynia, a painful perception of a light touch; and 5) formalin-induced hyperalgesia. Rats with short-term diabetes develop painful neuropathy, whereas those with longer-term diabetes and diabetic mice typically display manifestations of both painful and insensate neuropathy, or insensate neuropathy only. Animal studies using pharmacological and genetic approaches revealed important roles of increased aldose reductase, protein kinase C, and poly(ADPribose) polymerase activities, advanced glycation end-products and their receptors, oxidative-nitrosative stress, growth factor imbalances, and C-peptide deficiency in both painful and insensate neuropathy. This review describes recent achievements in studying the pathogenesis of diabetic neuropathic pain and sensory disorders in diabetic animal models and developing potential pathogenetic treatments. Key Words: Animal models, diabetic insensate neuropathy, diabetic painful neuropathy, formalin-induced hyperalgesia, mechanical hyper-and hypoalgesia, pathogenetic treatments of diabetic neuropathic pain and sensory loss, symptomatic treatments of diabetic pain, tactile allodynia, thermal hyper-and hypoalgesia.

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Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

Cited by 23 publications

References 35 publications

GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin

GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin

The protective role of prosaposin and its receptors in the nervous system

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

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