L-Serine, an Endogenous Amino Acid, Is a Potential Neuroprotective Agent for Neurological Disease and Injury

Abstract

Central nervous system (CNS) lesions are major causes of human death and disability worldwide, and they cause different extents of motor and sensory dysfunction in patients. Thus, it is crucial to develop new effective neuroprotective drugs and approaches targeted to the heterogeneous nature of CNS injury and disease. L-serine is an indispensable neurotrophic factor and a precursor for neurotransmitters. Although L-serine is a native amino acid supplement, its metabolic products have been shown to be essential not only for cell proliferation but also for neuronal development and specific functions in the brain. Growing evidence has suggested that L-serine regulates the release of several cytokines in the brain under some neuropathological conditions to recover cognitive function, improve cerebral blood flow, inhibit inflammation, promote remyelination and exert other neuroprotective effects on neurological injury. L-serine has also been used to treat epilepsy, schizophrenia, psychosis, and Alzheimer’s Disease as well as other neurological diseases. Furthermore, the dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine generally support the safety of L-serine. The high significance of this review lies in its emphasis on the therapeutic potential of using L-serine as a general treatment for numerous CNS diseases and injuries. Because L-serine performs a broad spectrum of functions, it may be clinically used as an effective neuroprotective agent.

RETRACTED: Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases

“…However, how this contributes to both structural and cognitive abnormalities is unknown. Growing evidence suggests that L-serine regulates the release of several cytokines in the brain to repair cognitive function, regulate cerebral blood flow, alleviate inflammation, enhance remyelination, and facilitate other neuroprotective effects on neurological impairments [87]. A recent study reveals that astrocytic glycolysis controls cognitive functions through synaptic NMDA receptors and suggests oral L-serine as an accessible therapy for AD [10].…”

Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus

“…L-serine is a substrate for the synthesis of proteins, phospholipids, particularly phosphatidylserine, and sphingolipids, such as ceramides, phosphosphingolipids, and glycosphingolipids, which are in large amounts in the white matter of the brain and in the myelin sheaths of nerves. L-serine acts as an agonist of the glycine receptor and, therefore, is classified as an inhibitory neurotransmitter [ 28 , 29 ]. L-serine, in reaction with homocysteine catalyzed by cystathionine β-synthase, initiates the transsulfuration pathway.…”

Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury

“…Present findings of day three-seven post injury elevations of certain plasma amino acids proved to be associated with less severe long-term microstructure outcomes, notably for cases of serine, arginine, asparagine, and phenylalanine, which are also known for their neuroprotective roles. Serine reduces neuroexcitotoxicity, regulates microglia polarization, decreases inflammation, improves cerebral blood flow and promotes survival, proliferation, and differentiation of neural stem cells (Ye et al, 2021). Arginine exerts a neuroprotective effect by suppression of the hypoxia inducible factor 1α (HIF-1α)/lactate dehydrogenase (LDHA)mediated inflammatory response in the microglia (Chen et al, 2020).…”