Results 11 to 20 of about 888 (137)

Aspartoacylase-lacZ knockin mice: an engineered model of Canavan disease. [PDF]

PLoS ONE, 2011
Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate.
Nadine Mersmann, Dmitri Tkachev, Ruth Jelinek, Philipp Thomas Röth, Wiebke Möbius, Torben Ruhwedel, Sabine Rühle, Wolfgang Weber-Fahr, Alexander Sartorius, Matthias Klugmann   +9 more
doaj   +6 more sources

Mapping the degradation pathway of a disease-linked aspartoacylase variant. [PDF]

PLoS Genetics, 2021
Canavan disease is a severe progressive neurodegenerative disorder that is characterized by swelling and spongy degeneration of brain white matter.
Sarah K Gersing, Yong Wang, Martin Grønbæk-Thygesen, Caroline Kampmeyer, Lene Clausen, Martin Willemoës, Claes Andréasson, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen   +9 more
doaj   +5 more sources

Aspartoacylase deficiency affects early postnatal development of oligodendrocytes and myelination [PDF]

Neurobiology of Disease, 2010
Canavan disease (CD) is a neurodegenerative disease, caused by a deficiency in the enzyme aspartoacylase (ASPA). This enzyme has been localized to oligodendrocytes; however, it is still undefined how ASPA deficiency affects oligodendrocyte development ...
Natalia S. Mattan, Cristina A. Ghiani, Marcia Lloyd, Reuben Matalon, Dean Bok, Patrizia Casaccia, Jean de Vellis   +6 more
doaj   +3 more sources

Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants [PDF]

Nature Communications
Unstable proteins are prone to form non-native interactions with other proteins and thereby may become toxic. To mitigate this, destabilized proteins are targeted by the protein quality control network. Here we present systematic studies of the cytosolic
Martin Grønbæk-Thygesen, Vasileios Voutsinos, Kristoffer E. Johansson, Thea K. Schulze, Matteo Cagiada, Line Pedersen, Lene Clausen, Snehal Nariya, Rachel L. Powell, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen   +12 more
doaj   +2 more sources

Central Dysmyelination in SSADH-Deficient Humans and Mice. [PDF]

Ann Clin Transl Neurol
ABSTRACT Objectives Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder characterized by an accumulation of γ‐aminobutyric (GABA). In addition to its synaptic role as an inhibitory neurotransmitter, GABA also plays an important role in myelination.
Tokatly Latzer I, Lee HHC, Yang E, Alves C, Bertoldi M, Fung C, Steele SV, Kule E, Jin Z, Rotenberg A, Roullet JB, Pearl PL.   +11 more
europepmc   +2 more sources

Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics, and Oncogenesis – Part 2: Acetate and ACSS2 in Health and Disease

Frontiers in Physiology, 2020
Acetate, the shortest chain fatty acid, has been implicated in providing health benefits whether it is derived from the diet or is generated from microbial fermentation of fiber in the gut.
John R. Moffett, Narayanan Puthillathu, Ranjini Vengilote, Diane M. Jaworski, Aryan M. Namboodiri   +4 more
doaj   +1 more source

Enhanced brain distribution of modified aspartoacylase [PDF]

Molecular Genetics and Metabolism, 2014
Canavan disease is a fatal neurological disorder caused by defects in the gene that produces the enzyme aspartoacylase. Enzyme replacement therapy can potentially be used to overcome these defects if a stable enzyme form that can gain access to the appropriate neural cells can be produced.
Nitesh K, Poddar, Stephen, Zano, Reka, Natarajan, Bryan, Yamamoto, Ronald E, Viola   +4 more
openaire   +2 more sources

Acetate Revisited: A Key Biomolecule at the Nexus of Metabolism, Epigenetics and Oncogenesis—Part 1: Acetyl-CoA, Acetogenesis and Acyl-CoA Short-Chain Synthetases

Frontiers in Physiology, 2020
Acetate is a major end product of bacterial fermentation of fiber in the gut. Acetate, whether derived from the diet or from fermentation in the colon, has been implicated in a range of health benefits.
John R. Moffett, Narayanan Puthillathu, Ranjini Vengilote, Diane M. Jaworski, Aryan M. Namboodiri   +4 more
doaj   +1 more source

Aspartoacylase Supports Oxidative Energy Metabolism during Myelination [PDF]

Journal of Cerebral Blood Flow & Metabolism, 2012
The inherited leukodystrophy Canavan disease arises due to a loss of the ability to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major point of focus for efforts to define NAA function. Accumulation of noncatabolized NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA associated with compromised ...
Jeremy S, Francis, Louise, Strande, Vladamir, Markov, Paola, Leone   +3 more
openaire   +2 more sources

N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase

Neurobiology of Disease, 2016
Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase ...
Jeremy S. Francis, PhD, Ireneusz Wojtas, PhD, Vladimir Markov, MD, Steven J. Gray, PhD, Thomas J. McCown, PhD, R. Jude Samulski, PhD, Larissa T. Bilaniuk, MD, Dah-Jyuu Wang, PhD, Darryl C. De Vivo, MD, Christopher G. Janson, MD, Paola Leone, PhD   +10 more
doaj   +1 more source