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"Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice.
Coughlan, Karen S; Mitchem, Mollie R; Hogg, Marion C; Prehn, Jochen HM
<p>This article is also available at <a href="http://www.neurobiologyofaging.org/article/S0197-4580(14)00628-9/abstract">http://www.neurobiologyofaging.org/article/S0197-4580(14)00628-9/abstract</a></p> <p>Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a master regulator of energy balance. As energy imbalance is documented as a key pathologic feature of amyotrophic lateral sclerosis (ALS), we investigated AMPK as a pharmacologic target in SOD1(G93A) mice. We noted a strong activation of AMPK in lumbar spinal cords of SOD1(G93A) mice. Pharmacologic activation of AMPK has shown protective effects in neuronal "preconditioning" models. We tested the hypothesis that "preconditioning" with a small molecule activator of AMPK, latrepirdine, exerts beneficial effects on disease progression. SOD1(G93A) mice (n = 24 animals per group; sex and litter matched) were treated with latrepirdine (1 μg/kg, intraperitoneal) or vehicle from postnatal day 70 to 120. Treatment with latrepirdine increased AMPK activity in primary mouse motor neuron cultures and in SOD1(G93A) lumbar spinal cords. Mice "preconditioned" with latrepirdine showed a delayed symptom onset and a significant increase in life span (p < 0.01). Our study suggests that "preconditioning" with latrepirdine may represent a possible therapeutic strategy for individuals harboring ALS-associated gene mutations who are at risk for developing ALS.</p>
Keyword(s): Amyotrophic Lateral Sclerosis; AMPK; Bioenergetics; Pre-Conditioning; Spinal Cord; Motoneuron Degeneration; SOD1; Physics; Physiology
Publication Date:
2015
Type: Journal article
Peer-Reviewed: Yes
Institution: Royal College of Surgeons in Ireland
Citation(s): Coughlan KS, Mitchem MR, Hogg MC, Prehn JHM. "Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiology of Aging. 2015;36(2):1140-50.
Publisher(s): Pergamon Press
File Format(s): application/pdf
Related Link(s): http://epubs.rcsi.ie/physiolart/61/
First Indexed: 2015-07-31 15:36:37 Last Updated: 2018-02-13 07:20:07