The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy

W. Zhang; Y. Murakawa; K. M. Wozniak; B. Slusher; A. A.F. Sima

doi:10.1016/j.jns.2006.05.052

The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy

W. Zhang, Y. Murakawa, K. M. Wozniak, B. Slusher, A. A.F. Sima

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

49 Scopus citations

Abstract

Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.

Original language	English (US)
Pages (from-to)	217-223
Number of pages	7
Journal	Journal of the Neurological Sciences
Volume	247
Issue number	2
DOIs	https://doi.org/10.1016/j.jns.2006.05.052
State	Published - Sep 25 2006
Externally published	Yes

Keywords

BB/Wor rat
GCPII inhibition
Nociception
Sensory diabetic neuropathy

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1016/j.jns.2006.05.052

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title = "The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy",

abstract = "Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.",

keywords = "BB/Wor rat, GCPII inhibition, Nociception, Sensory diabetic neuropathy",

author = "W. Zhang and Y. Murakawa and Wozniak, {K. M.} and B. Slusher and Sima, {A. A.F.}",

note = "Funding Information: This study was supported by MGI Pharma. Dr. Murakawa was supported by a post-doc. fellowship from the Thomas Foundation. ",

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T1 - The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy

AU - Zhang, W.

AU - Murakawa, Y.

AU - Wozniak, K. M.

AU - Slusher, B.

AU - Sima, A. A.F.

N1 - Funding Information: This study was supported by MGI Pharma. Dr. Murakawa was supported by a post-doc. fellowship from the Thomas Foundation.

PY - 2006/9/25

Y1 - 2006/9/25

N2 - Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.

AB - Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.

KW - BB/Wor rat

KW - GCPII inhibition

KW - Nociception

KW - Sensory diabetic neuropathy

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The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy

Abstract

Keywords

ASJC Scopus subject areas

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