John P. Crow, Ph.D.

Phone: (501) 526-7301
Fax: (501) 686-5521


M.S. –  Auburn University School of Pharmacy, 1985
PhD. – Univ. of South Alabama, 1991

Research Interests

Dr. Crow has been involved in ALS therapeutics development and pathogenesis for over 20 years, first with in vitro approaches aimed at identifying toxic functions of SOD1 mutants, and later with both therapeutic and mechanistic studies in G93A mice and rats, and G37R mice.  Dr. Crow and co-workers were the first to show altered zinc binding of SOD1 mutants, and proposed a common toxic mechanism for SOD1 involving a zinc-deficient intermediate.  Zinc-deficient SOD1 – whether derived from mutant or wild-type – has  both pro-oxidant and pro-aggregatory properties, and offers a mechanism whereby most forms of ALS could be caused by SOD1.   Another toxic mechanism examined in the lab involves the “abnormal” amino acid D-serine, which is a co-agonist at NMDA receptors.  D-serine provides an alternative mechanism for induction of glutmate excitotoxicity, and altering D-serine (endogenously or exogenously) was shown to dramatically affect onset and duration of ALS symptoms in G93A mice.  In 2006 Dr. Crow began an effort to identify novel ALS therapeutics; that effort evolved into an ALS Center, which was formally dedicated the J. Thomas May Center for ALS Research and Translational Medicine in 2008.  Over the next eight years, many different classes of FDA-approved drugs, nutraceuticals, experimental compounds, and combinations (218 in all) were tested in G93A and G37R mice.   The most promising compounds were found to be from botanical sources, leading Dr. Crow to examine other medicinal plant sources for the presence of novel therapeutics and nutraceuticals.  Other ongoing work in lab involves identification and characterization of oxidative modifications to drugs and endogenous biomolecules.  Drugs and biomolecules which possess phenolic rings can undergo radical reactions leading to metabolites with novel biological activities.  The working hypothesis is that metabolites derived from oxidative modifications may play a role in the overall pharmacology and/or toxicology of the parent compounds.  As part of this effort, Dr. Crow is actively collaborating with several other groups to identify, characterize, and quantify novel metabolites in other human disease conditions.

Recent Research Support

Completed Research
NIH/NINDS 2R01NS040819-05  (12/01/00 – 04/30/13)
Mechanisms of Protection and Pathogenesis in ALS Mice.

NIH R01NS40819 (06/02/03 – 05/31/06)
Mechanism of Selective Toxicity of SOD Mutants in ALS


Marecki JC, Parajuli N, Crow, JP, MacMillan-Crow LA, The Use of the Cre/loxP System to Study Oxidative Stress in Tissue-Specific MnSOD Knockout Models. Invited Review.  Antioxidant Redox Signal, 2013, [epub ahead of print] (PMID: 23641945).

Crow JP, Marecki JC, Thompson M.  D-Serine Production, Degradation, and Transport in ALS:  Critical Role of Methodology.  Neural Res Int. (625245), 2013 (PMID: 23029613).

Thompson M, Marecki JC, Marinesco S, Labrie V, Roder JC, Barger SW, Crow JP. Paradoxical roles of serine racemase and D-serine in the G93A mSOD1 mouse model of amyotrophic lateral sclerosis. J.Neurochem. 120 (4):598-610, 2012 (PMID: 22117694).

MacMillan-Crow LA, Crow, JP. Does More MnSOD Mean More Hydrogen Peroxide?  Anti-Cancer Agents in Medicinal Chemistry, Anticancer Agents Med Chem. Feb;11(2):178-80, 2011 (PMID: 21291402).

Bhogaraju VK, Levi MS, Reed RL, Crow JP, Rapid one-step purification of native dimeric ALS-associated human Cu/Zn superoxide dismutase from transgenic rat tissues.  Amyotroph Lateral Scler 11(3): 283-288, 2010 (PMID: 9929749).

Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL. The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J.Neurochem. 101 (1):87-98, 2007 (PMID: 17241118).

Petri S, Kiaei M, Kipiani K, Chen J, Calingasan NY, Crow JP, Beal MF. Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotropic lateral sclerosis, Neurobiol. Dis., 22:40-49, 2006  (PMID: 16289867).

Crow JP. Catalytic antioxidants to treat amyotropic lateral sclerosis. Expert.Opin.Investig.Drugs 15 (11):1383-1393, 2006 (PMID:17040198).

Zhang H, JosephJ, Crow JP, Kalyanaraman B. Mass spectral evidence for carbonate-anion-radical-induced posttranslational modification of tryptophan to kynurenine in human Cu, Zn superoxide dismutase. Free Radic.Biol.Med. 37:2018-26, 2004 (PMID: 15544920).

Zhang H, Andrekopoulos C, Joseph J Crow JP, Kalyanaraman B. The carbonate radical anion-induced covalent aggregation of human copper, zinc superoxide dismutase, and alpha-synuclein: intermediacy of tryptophan- and tyrosine-derived oxidation products. Free Radic. Biology Medical 36:1355-1365, 2004 (PMID: 15135171).

View Dr. Crow’s Publication List