L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies

Chiechio, Santina; Copani, Agata; Nicoletti, Ferdinando; Gereau, Robert W.

doi:10.2174/157015906778019509

Cited by 36 publications

(27 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its metabolite, carnitine, is used to transport fatty acids into the mitochondria for β - oxidation, and acetyl - L-carnitine regulates the activities of several Krebs cycle enzymes, contributes to the regulation of mitochondrial membrane lipid composition, enhances glutathione levels, and is itself an antioxidant. 74 …”

Section: Implications For Therapymentioning

confidence: 99%

Mitotoxicity in distal symmetrical sensory peripheral neuropathies

2014

View full text Add to dashboard Cite

Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor—that is, intraepidermal nerve fibres—of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions.

show abstract

Section: Implications For Therapymentioning

confidence: 99%

Mitotoxicity in distal symmetrical sensory peripheral neuropathies

2014

View full text Add to dashboard Cite

show abstract

“…ALCAR has several properties that could have neuroprotective effects including providing carnitine and an acyl moiety that can be used for energy [57, 100], and for synthesis of acetylcholine [101], amino acid neurotransmitters [57] and lipids [102] as discussed in more detail below. ALCAR has been found to have anti-inflammatory effects [7], lead to stabilization of membranes [1], act as an antioxidant protecting against oxidative stress [37, 53, 103, 104], enhance the activity of nerve growth factor [105], and potentiate energy metabolism [57, 97], and cholinergic responses [1, 106]. ALCAR administration induced mitochondrial biogenesis in hypoxic rats [15], and increased mitochondrial mass after spinal cord injury [13].…”

Section: Neuroprotection By Acetyl-l-carnitine (Alcar)mentioning

confidence: 99%

l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain

2017

View full text Add to dashboard Cite

L-Carnitine functions to transport long chain fatty acyl CoAs into the mitochondria for degradation by β-oxidation. Treatment with L-carnitine can ameliorate metabolic imbalance in many inborn errors of metabolism. In recent years there has been considerable interest in the therapeutic potential of L-carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for neuroprotection in a number of disorders including hypoxia-ischemia, traumatic brain injury, Alzheimer’s disease and in conditions leading to central or peripheral nervous system injury. There is compelling evidence from preclinical studies that L-carnitine and ALCAR can improve energy status, decrease oxidative stress and prevent subsequent cell death in models of adult, neonatal and pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized for energy, used as a precursor for acetylcholine, or incorporated into glutamate, glutamine and GABA, or into lipids for myelination and cell growth. Administration of ALCAR after brain injury in rat pups improved long-term functional outcomes, including memory. Additional studies are needed to better explore the potential of L-carnitine and ALCAR for protection of developing brain as there is an urgent need for therapies that can improve outcome after neonatal and pediatric brain injury.

show abstract

“…Further to this, in rodents ALC up-regulates the expression of metabotropic glutamate receptor 2 (mGlu2) in dorsal root ganglia (DRG) of the spinal cord with a mechanism demonstrated to be dependent on activation of the NF-kappaB pathway through acetylation of p65/RelA. On the basis of this action ALC is suggested for clinical management of neuropathic pain [209][210][211].…”

Section: The Carnitine System: Physiological Roles Insufficiency Andmentioning

confidence: 99%

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

et al. 2010

View full text Add to dashboard Cite

The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. A prediction of this theory is that, among species, differential rates of aging may be apparent on the basis of intrinsic differences in oxidative damage accrual. Although widely accepted, there is a growing number of exceptions to this theory, most contingently related to genetic model organism investigations. Proteins are one of the prime targets for oxidative damage and cysteine residues are particularly sensitive to reversible and irreversible oxidation. The adaptation and survival of cells and organisms requires the ability to sense proteotoxic insults and to coordinate protective cellular stress response pathways and chaperone networks related to protein quality control and stability. The toxic effects that stem from the misassembly or aggregation of proteins or peptides, in any cell type, are collectively termed proteotoxicity. Despite the abundance and apparent capacity of chaperones and other components of homeostasis to restore folding equilibrium, the cell appears poorly adapted for chronic proteotoxic stress which increases in cancer, metabolic and neurodegenerative diseases. Pharmacological modulation of cellular stress response pathways has emerging implications for the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. A critical key to successful medical intervention is getting the dose right. Achieving this goal can be extremely challenging due to human inter-individual variation as affected by age, gender, diet, exercise, genetic factors and health status. The nature of the dose response in and adjacent to the therapeutic zones, over the past decade has received considerable advances. The hormetic dose-response, challenging long-standing beliefs about the nature of the dose-response in a lowdose zone, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses, including carnitines. This paper describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including the possible signaling mechanisms by which the carnitine system, by interplaying metabolism, mitochondrial energetics and activation of critical vitagenes, modulates signal transduction cascades that confer cytoprotection against chronic degenerative damage associated to aging and neurodegenerative disorders.

show abstract

L-Acetylcarnitine: A Proposed Therapeutic Agent for Painful Peripheral Neuropathies

Cited by 36 publications

References 51 publications

Mitotoxicity in distal symmetrical sensory peripheral neuropathies

Mitotoxicity in distal symmetrical sensory peripheral neuropathies

l-Carnitine and Acetyl-l-carnitine Roles and Neuroprotection in Developing Brain

Cellular Stress Responses, Mitostress and Carnitine Insufficiencies as Critical Determinants in Aging and Neurodegenerative Disorders: Role of Hormesis and Vitagenes

Contact Info

Product

Resources

About