Carnitine, carnitine acetyltransferase, and glutathione in Alzheimer brain (original) (raw)
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Carnitine, Carnitine Acyltransferases, and Rat Brain Function
The concentrations of free, short chain, and long chain acylcamitines and the enzyme activities of camitine acetyltransferase (CAT) and carnitine palmityltransferase (CPT) were studied in different rat brain regions. The fate of tritium-labeled camitine was studied in different brain regions in vivo after i.p. injection in 3-monthold Sprague-Dawley rats. The tritium counts were particularly high in the hypothalamic region. At 24 h after hydrocortisone injection, a significant increase in counts was observed in the hypothalamus (P < 0.0 1). A high concentration of total camitine was found in the hypothalamus (4.00 nmol/mg noncollagen protein) and in other regions such as the spinal cord (1.29 nmol/mg noncollagen protein), cerebellum (1.19), and olfactory tracts (0.66) camitine concentration was much lower. Camitine content was proportional to CPT, an inner mitochondrial enzyme. The activity of the enzyme CAT was found to be high in rat hippocampus and hypothalamus. This enzyme in brain may be involved in the transport of acyl groups outside the mitochondria and in the regulation of pyruvate utilization, contributing to acetylcholine synthesis or regulation.
The role of L-carnitine in neurodegenerative disorders
Pharmakeutiki, 2009
Population ageing and modern lifestyle seem to be two important factors contributing to neurodegenerative diseases, while the underlying cellular pathophysiological mechanisms implicate the phenomenon of oxidative stress in most studies. Antioxidants such as carnitine, which neutralize directly or indirectly the action of free radicals, are suggested as pharmacological compounds which could limit these degenerative processes. In this review, we present the laboratory and clinical data on the protective effect of L-carnitine administration in neurodegenerative diseases, such as Alzheimer disease, Parkinson disease and multiple sclerosis. In addition, the potential role of carnitine in limiting degenerative events accompanying ageing, such as the decline in hearing or vision, or in limiting geriatric psychiatric diseases, is also examined.
Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update
Nutrients, 2020
Several studies explored the effects of acetyl-L-carnitine (ALC) in dementia, suggesting a role in slowing down cognitive decline. Nevertheless, in 2003 a systematic review concluded there was insufficient evidence to recommend a clinical use, although a meta-analysis in the same year showed a significant advantage for ALC for clinical scales and psychometric tests. Since then, other studies have been published; however, a critical review is still lacking. We provide an update of the studies on ALC in primary and secondary dementia, highlighting the current limitations and translational implications. Overall, the role of ALC in dementia is still under debate. The underlying mechanisms may include restoring of cell membranes and synaptic functioning, enhancing cholinergic activity, promoting mitochondrial energy metabolism, protecting against toxins, and exerting neurotrophic effects. The effects of ALC on the gut–liver–brain axis seem to identify the category of patients in which th...
Annals of the New York Academy of Sciences, 2004
L-carnitine and acetyl-L-carnitine (ALC) are both used to improve mitochondrial function. Although it has been argued that ALC is better than l-carnitine in absorption and activity, there has been no experiment to compare the two compounds at the same dose. In the present experiment, the effects of ALC and L-carnitine on the levels of free, acyl, and total L-carnitine in plasma and brain, rat ambulatory activity, and biomarkers of oxidative stress are investigated. Aged rats (23 months old) were given ALC or L-carnitine at 0.15% in drinking water for 4 weeks. L-carnitine and ALC were similar in elevating carnitine levels in plasma and brain. Both increased ambulatory activity similarly. However, ALC decreased the lipid peroxidation (malondialdehyde, MDA) in the old rat brain, while L-carnitine did not. ALC decreased the extent of oxidized nucleotides (oxo8dG/oxo8G) immunostaining in the hippocampal CA1 and cortex, while L-carnitine did not. ALC decreased nitrotyrosine immunostaining in the hippocampal CA1 and white matter, while L-carnitine did not. In conclusion, ALC and L-carnitine were similar in increasing ambulatory activity in old rats and elevating carnitine levels in blood and brain. However, ALC was effective, unlike L-carnitine, in decreasing oxidative damage, including MDA, oxo8dG/oxo8G, and nitrotyrosine, in old rat brain. These data suggest that ALC may be a better dietary supplement than L-carnitine.
Molecular Neurobiology, 2009
Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, is a naturally occurring substance that when administered at supraphysiological concentrations is neuroprotective. ALC plays an essential role in intermediary and mitochondrial metabolism. It has also neurotrophic and antioxidant actions. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various etiologies, and it is a molecule of considerable interest for its clinical application in various neural disorders, such as Alzheimer's disease and painful neuropathies, although little is known regarding the effects of ALC on gene expression. Suppression subtractive hybridization methodology was used for the generation of subtracted complementary DNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after a chronic ALC treatment. In the present paper, we provide evidences for the up-regulation of the expression of prostaglandin D 2 synthase, brain-specific Na + -dependent inorganic phosphate transporter, and cytochrome b oxidase, bc1 complex induced in the rat brain by ALC. On the contrary, ALC treatment downregulates the expression of the gene of ferritin-H. Altogether, these results suggest that ALC might play a cytoprotective role against various brain stressors.
European Journal of Pharmacology, 2008
Alzheimer Disease is the most common chronic neurodegenerative disorder associated with aging. Nevertheless, its pharmacological therapy is still an unresolved issue. In double-blind controlled studies, acetyl-L-carnitine (ALC) demonstrated beneficial effects on Alzheimer's disease. However, the mechanisms behind its neuroprotective ability remain to be fully established. In this study, the effect of acetyl-L-carnitine on amyloid precursor protein (APP) metabolism was investigated by in vitro models, both in a neuroblastoma cell line and in primary hippocampal cultures. We found that ALC treatment stimulates α-secretase activity and physiological APP metabolism. In particular, ALC favors the delivery of ADAM10 (a disintegrin and metalloproteinase 10, the most accredited candidate for α-secretase) to the post-synaptic compartment, and consequently positively modulates its enzymatic activity towards APP. Our findings suggest that the benefits of ALC reported in previous clinical studies are underscored by the specific biological mechanism of this compound on APP metabolism. In fact, ALC can directly influence the primary event in Alzheimer's disease pathogenesis, i.e. the Amyloid β cascade, promoting α-secretase activity and directly affecting the release of the non amyloidogenic metabolite.
The role of L-carnitine in the brain aging
Pharmakeftiki, 2009
Carnitine is an important compound of cellular metabolism and it is essential for b-oxidation of lipid acids. In neural system, although b-oxidation is not the main source of energy, carnitine is involved in the regulation of energy production and calorie intake, the latter via the hypothalamus, as well as indirectly in synaptic neurotransmission. Since the above cellular processes are modified during brain aging, we aimed to review the literature on the role of carnitine in brain aging. Particular emphasis is given on the mechanisms of antioxidative action of carnitine in brain, as well as its association with cholinergic and dopaminergic system along with other various neural membrane receptors, such as the NMDA, calcium or nerve growth factor (NGF) receptors. In addition, the connection of carnitine with mechanisms of protection against cellular stress and particularly its relation with heat shock proteins (HSP), ionic channels and sodium pump, is also reviewed.
Preventive Role of L-Carnitine and Balanced Diet in Alzheimer’s Disease
Nutrients
The prevention or alleviation of neurodegenerative diseases, including Alzheimer’s disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious...