Treatment of diabetic neuropathy with a novel PAR1-targeting molecule

Efrat Shavit-Stein; Shany Guly Gofrit; Alexandra Gayster; Yotam Teldan; Ariel Ron; Eiman Abu Bandora; Valery Golderman; Orna Gera; Sagi Harnof; Joab Chapman; Amir Dori

doi:https://doi.org/10.3390/biom10111552

Treatment of diabetic neuropathy with a novel PAR1-targeting molecule

Efrat Shavit-Stein, Shany Guly Gofrit, Alexandra Gayster, Yotam Teldan, Ariel Ron, Eiman Abu Bandora, Valery Golderman, Orna Gera, Sagi Harnof, Joab Chapman, Amir Dori

Tel Aviv University

Research output: Contribution to journal › Article › peer-review

Abstract

Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.

Original language	English
Article number	1552
Pages (from-to)	1-11
Number of pages	11
Journal	Biomolecules
Volume	10
Issue number	11
DOIs	https://doi.org/10.3390/biom10111552
State	Published - Nov 2020

Keywords

Diabetes mellitus
PAR1
Peripheral neuropathy
Streptozotocin
Thrombin

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.3390/biom10111552

Cite this

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title = "Treatment of diabetic neuropathy with a novel PAR1-targeting molecule",

abstract = "Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.",

keywords = "Diabetes mellitus, PAR1, Peripheral neuropathy, Streptozotocin, Thrombin",

author = "Efrat Shavit-Stein and Gofrit, {Shany Guly} and Alexandra Gayster and Yotam Teldan and Ariel Ron and Bandora, {Eiman Abu} and Valery Golderman and Orna Gera and Sagi Harnof and Joab Chapman and Amir Dori",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = nov,

doi = "https://doi.org/10.3390/biom10111552",

language = "الإنجليزيّة",

volume = "10",

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TY - JOUR

T1 - Treatment of diabetic neuropathy with a novel PAR1-targeting molecule

AU - Shavit-Stein, Efrat

AU - Gofrit, Shany Guly

AU - Gayster, Alexandra

AU - Teldan, Yotam

AU - Ron, Ariel

AU - Bandora, Eiman Abu

AU - Golderman, Valery

AU - Gera, Orna

AU - Harnof, Sagi

AU - Chapman, Joab

AU - Dori, Amir

PY - 2020/11

Y1 - 2020/11

N2 - Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.

AB - Diabetic peripheral neuropathy (DPN) is a disabling common complication of diabetes mellitus (DM). Thrombin, a coagulation factor, is increased in DM and affects nerve function via its G-protein coupled protease activated receptor 1 (PAR1). Methods: A novel PAR1 modulator (PARIN5) was designed based on the thrombin PAR1 recognition site. Coagulation, motor and sensory function and small fiber loss were evaluated by employing the murine streptozotocin diabetes model. Results: PARIN5 showed a safe coagulation profile and showed no significant effect on weight or glucose levels. Diabetic mice spent shorter time on the rotarod (p <0.001), and had hypoalgesia (p <0.05), slow conduction velocity (p <0.0001) and reduced skin innervation (p <0.0001). Treatment with PARIN5 significantly improved rotarod performance (p <0.05), normalized hypoalgesia (p <0.05), attenuated slowing of nerve conduction velocity (p <0.05) and improved skin innervation (p <0.0001). Conclusion: PARIN5 is a novel pharmacological approach for prevention of DPN development, via PAR1 pathway modulation.

KW - Diabetes mellitus

KW - PAR1

KW - Peripheral neuropathy

KW - Streptozotocin

KW - Thrombin

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Treatment of diabetic neuropathy with a novel PAR1-targeting molecule

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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