Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Autor:	Koza LA; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA., Winter AN; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA., Holsopple J; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA., Baybayon-Grandgeorge AN; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA., Pena C; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA., Olson JR; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA., Mazzarino RC; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA., Patterson D; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA.; Eleanor Roosevelt Institute, University of Denver, 2101 E. Wesley Ave, Denver, CO 80210, USA., Linseman DA; Department of Biological Sciences, F. W. Olin Hall, Room 102, University of Denver, 2190 E. Iliff Ave, Denver, CO 80208, USA.; Knoebel Institute for Healthy Aging, Engineering Computer Science, Suite 579, University of Denver, 2155 E. Wesley Ave, Denver, CO 80208, USA.; Eleanor Roosevelt Institute, University of Denver, 2101 E. Wesley Ave, Denver, CO 80210, USA.
Jazyk:	angličtina
Zdroj:	Nutrients [Nutrients] 2020 Jun 18; Vol. 12 (6). Date of Electronic Publication: 2020 Jun 18.
DOI:	10.3390/nu12061824
Abstrakt:	Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by motor neuron apoptosis and subsequent skeletal muscle atrophy caused by oxidative and nitrosative stress, mitochondrial dysfunction, and neuroinflammation. Anthocyanins are polyphenolic compounds found in berries that possess neuroprotective and anti-inflammatory properties. Protocatechuic acid (PCA) is a phenolic acid metabolite of the parent anthocyanin, kuromanin, found in blackberries and bilberries. We explored the therapeutic effects of PCA in a transgenic mouse model of ALS that expresses mutant human Cu, Zn-superoxide dismutase 1 with a glycine to alanine substitution at position 93. These mice display skeletal muscle atrophy, hindlimb weakness, and weight loss. Disease onset occurs at approximately 90 days old and end stage is reached at approximately 120 days old. Daily treatment with PCA (100 mg/kg) by oral gavage beginning at disease onset significantly extended survival (121 days old in untreated vs. 133 days old in PCA-treated) and preserved skeletal muscle strength and endurance as assessed by grip strength testing and rotarod performance. Furthermore, PCA reduced astrogliosis and microgliosis in spinal cord, protected spinal motor neurons from apoptosis, and maintained neuromuscular junction integrity in transgenic mice. PCA lengthens survival, lessens the severity of pathological symptoms, and slows disease progression in this mouse model of ALS. Given its significant preclinical therapeutic effects, PCA should be further investigated as a treatment option for patients with ALS. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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