title: Behavioral and neurochemical effects of proline.
abstract: Proline is an amino acid with an essential role for primary metabolism and physiologic functions. Hyperprolinemia results from the deficiency of specific enzymes for proline catabolism, leading to tissue accumulation of this amino acid. Hyperprolinemic patients can present neurological symptoms and brain abnormalities, whose aetiopathogenesis is poorly understood. This review addresses some of the findings obtained, mainly from animal studies, indicating that high proline levels may be associated to neuropathophysiology of some disorders. In this context, it has been suggested that energy metabolism deficit, Na(+),K(+)-ATPase, kinase creatine, oxidative stress, excitotoxicity, lipid content, as well as purinergic and cholinergic systems are involved in the effect of proline on brain damage and spatial memory deficit. The discussion focuses on the relatively low antioxidant defenses of the brain and the vulnerability of neural tissue to reactive species. This offers new perspectives for potential therapeutic strategies for this condition, which may include the early use of appropriate antioxidants as a novel adjuvant therapy, besides the usual treatment based on special diets poor in proline.
authors.affiliation: Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil. wyse@ufrgs.br
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000172:deficiency; D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D001928:Brain Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005609:Free Radicals / Q000009:adverse effects*; D005998:Glycine / Q000378:metabolism / Q000652:urine; D015799:Gyrate Atrophy / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D011392:Proline / Q000009:adverse effects / Q000378:metabolism; D011394:Proline Oxidase / Q000172:deficiency / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D015499:Renal Tubular Transport, Inborn Errors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; D014810:Vitamin E; D011392:Proline; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D011394:Proline Oxidase; D003402:Creatine Kinase; D000254:Sodium-Potassium-Exchanging ATPase; D001205:Ascorbic Acid; D005998:Glycine