In excitotoxicity,

nerve cells A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

suffer damage or death when the levels of otherwise necessary and safe

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s such as

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

become pathologically high, resulting in excessive stimulation of

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

. For example, when

glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...

s such as the

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Different mechanisms might lead to increased extracellular glutamate concentrations, e.g. reduced uptake by glutamate transporters (EAATs), synaptic hyperactivity, or abnormal release from different neural cell types. Excess glutamate allows high levels of

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

ions (Ca²⁺) to enter the cell. Ca²⁺ influx into cells activates a number of enzymes, including

phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze: *Phospholipase ...

endonuclease In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...

s, and

proteases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

such as calpain. These enzymes go on to damage cell structures such as components of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

, and DNA. In evolved,

complex adaptive system A complex adaptive system (CAS) is a system that is ''complex'' in that it is a dynamic network of interactions, but the behavior of the ensemble may not be predictable according to the behavior of the components. It is '' adaptive'' in that the ...

s such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA, in subtoxic amounts, can block glutamate toxicity and thereby induce neuronal survival. Excitotoxicity may be involved in

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Symptoms of ...

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity ranging from mild traumatic brain injury (mTBI/concussion) to severe traumati ...

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spo ...

(through noise overexposure or

ototoxicity Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and tempora ...

), and in

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

such as

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(ALS),

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

alcohol withdrawal Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in or cessation of alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, a ...

hyperammonemia Hyperammonemia, or high ammonia levels, is a metabolic disturbance characterised by an excess of ammonia in the blood. Severe hyperammonemia is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammoni ...

and especially over-rapid

benzodiazepine withdrawal Benzodiazepine withdrawal syndrome (BZD withdrawal) is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stop ...

, and also

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

.Kim AH, Kerchner GA, and Choi DW. Blocking Excitotoxicity or Glutamatergic Storm. Chapter 1 in ''CNS Neuroprotection''. Marcoux FW and Choi DW, editors. Springer, New York. 2002. Pages 3-36 Other common conditions that cause excessive glutamate concentrations around neurons are

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

. Blood sugars are the primary energy source for glutamate removal from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose (dextrose) IV drip during excitotoxic shock to avoid a dangerous build up of glutamate around NMDA and AMPA neurons. When 5% glucose (dextrose) IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. and "status epilepticus can also be triggered by a build up of glutamate around inter-synaptic neurons."

History

The harmful effects of glutamate on the

were first observed in 1954 by T. Hayashi, a Japanese scientist who stated that direct application of glutamate caused

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

activity, though this report went unnoticed for several years. D. R. Lucas and J. P. Newhouse, after noting that "single doses of sodium glutamate in humans">Monosodium_glutamate.html" ;"title="0–30 grams of Monosodium glutamate">sodium glutamate in humanshave ... been administered intravenously without permanent ill-effects", observed in 1957 that a subcutaneous dose described as "a little less than lethal", destroyed the neurons in the inner layers of the

Subcutaneous injection">subcutaneous dose described as "a little less than lethal", destroyed the neurons in the inner layers of the retina in newborn mouse">mice A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

. In 1969, John Olney discovered that the phenomenon was not restricted to the retina, but occurred throughout the brain, and coined the term excitotoxicity. He also assessed that cell death was restricted to postsynaptic neurons, that glutamate

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s were as

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

as their efficiency to activate glutamate receptors, and that glutamate

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. In 2002, Hilmar Bading and co-workers found that excitotoxicity is caused by the activation of

s located outside synaptic contacts. The molecular basis for toxic extrasynaptic NMDA receptor signaling was uncovered in 2020 when Hilmar Bading and co-workers described a death signaling complex that consists of extrasynaptic NMDA receptor and TRPM4. Disruption of this complex using NMDAR/TRPM4 interface inhibitors (also known as 'interface inhibitors‘) renders extrasynaptic NMDA receptor non-toxic.

Pathophysiology

Excitotoxicity can occur from substances produced within the body (

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the central nervous system of mammals.Temple MD, O'Leary DM, and Faden AI. The role of glutamate receptors in the pathophysiology of traumatic CNS injury. Chapter 4 in ''Head Trauma: Basic, Preclinical, and Clinical Directions''. Miller LP and Hayes RL, editors. Co-edited by Newcomb JK. John Wiley and Sons, Inc. New York. 2001. Pages 87-113. During normal conditions, glutamate

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

can be increased up to 1 mM in the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...

, which is rapidly decreased in the lapse of milliseconds. When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. This pathologic phenomenon can also occur after

brain injury Brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating trauma-induced damage. A common ...

and

. Within minutes after spinal cord injury, damaged neural cells within the lesion site spill glutamate into the extracellular space where glutamate can stimulate presynaptic glutamate receptors to enhance the release of additional glutamate. Brain trauma or

can cause

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

, in which

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

flow is reduced to inadequate levels. Ischemia is followed by accumulation of glutamate and

aspartate Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protein ...

in the

extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women and the obese typically ha ...

, causing cell death, which is aggravated by lack of

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

and

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

. The

biochemical cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...

resulting from ischemia and involving excitotoxicity is called the ischemic cascade. Because of the events resulting from ischemia and glutamate receptor activation, a deep chemical coma may be induced in patients with brain injury to reduce the metabolic rate of the brain (its need for oxygen and glucose) and save energy to be used to remove glutamate actively. (The main aim in induced comas is to reduce the

intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury ( mmHg) and at rest, is normally 7–15 mmHg for a supine adu ...

, not brain

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

). Increased extracellular glutamate levels leads to the activation of Ca²⁺ permeable NMDA receptors on myelin sheaths and

oligodendrocytes Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axon ...

, leaving oligodendrocytes susceptible to Ca²⁺ influxes and subsequent excitotoxicity. One of the damaging results of excess calcium in the cytosol is initiating apoptosis through cleaved

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyste ...

processing. Another damaging result of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

and other proteins that can lead to

. The pore can also cause mitochondria to release more calcium. In addition, production of

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(ATP) may be stopped, and

ATP synthase ATP synthase is an enzyme that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). ATP synthase is a molecular machine. The overall reaction catalyzed ...

may in fact begin hydrolysing ATP instead of producing it, which is suggested to be involved in depression. Inadequate ATP production resulting from brain trauma can eliminate

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in Concentration, solute concentration across ...

s of certain ions.

Glutamate transporter Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the ex ...

s require the maintenance of these ion gradients to remove glutamate from the extracellular space. The loss of ion gradients results in not only the halting of glutamate uptake, but also in the reversal of the transporters. The Na⁺-glutamate transporters on neurons and astrocytes can reverse their glutamate transport and start secreting glutamate at a concentration capable of inducing excitotoxicity. This results in a buildup of glutamate and further damaging activation of glutamate receptors. On the

molecular A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry, ...

level, calcium influx is not the only factor responsible for apoptosis induced by excitoxicity. Recently, it has been noted that extrasynaptic NMDA receptor activation, triggered by both glutamate exposure or hypoxic/ischemic conditions, activate a

CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...

( cAMP response element binding)

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

shut-off, which in turn caused loss of

mitochondrial membrane A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

potential and apoptosis. On the other hand, activation of synaptic NMDA receptors activated only the CREB pathway, which activates

BDNF Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...

(brain-derived neurotrophic factor), not activating apoptosis.

Exogenous excitotoxins

Exogenous excitotoxins refer to neurotoxins that also act at postsynaptic cells but are not normally found in the body. These toxins may enter the body of an organism from the environment through wounds, food intake, aerial dispersion etc. Common excitotoxins include glutamate analogs that mimic the action of glutamate at glutamate receptors, including AMPA and NMDA receptors.

BMAA

The L-alanine derivative β-methylamino-L-alanine ( BMAA) has long been identified as a

neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...

which was first associated with the

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

–

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

complex (

Lytico-bodig disease Lytico-Bodig (also Lytigo-bodig) disease, Guam disease, amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), and Western Pacific amyotrophic lateral sclerosis-parkinsonism-dementia complex is a rare, terminal neurodegenerative dis ...

) in the

Chamorro people The Chamorro people (; also Chamoru) are the Indigenous peoples of Oceania, Indigenous people of the Mariana Islands, politically divided between the Territories of the United States, United States territory of Guam and the encompassing Norther ...

of Guam. The widespread occurrence of BMAA can be attributed to

cyanobacteria Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteri ...

which produce BMAA as a result of complex reactions under nitrogen stress. Following research, excitotoxicity appears to be the likely mode of action for BMAA which acts as a

agonist, activating

AMPA α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate Glutamic acid (symbol Glu or E; kn ...

and

NMDA ''N''-methyl--aspartic acid, or ''N''-methyl--aspartate (NMDA), is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unl ...

receptors and causing damage to cells even at relatively low concentrations of 10 μM. The subsequent uncontrolled influx of Ca²⁺ then leads to the pathophysiology described above. Further evidence of the role of BMAA as an excitotoxin is rooted in the ability of NMDA antagonists like MK801 to block the action of BMAA. More recently, evidence has been found that BMAA is misincorporated in place of L-serine in human proteins. A considerable portion of the research relating to the toxicity of BMAA has been conducted on

rodents Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...

. A study published in 2016 with vervets (Chlorocebus sabaeus) in St. Kitts, which are homozygous for the apoE4 (APOE-ε4) allele (a condition which in humans is a risk factor for Alzheimer's disease), found that vervets orally administered BMAA developed hallmark histopathology features of Alzheimer's Disease including amyloid beta plaques and neurofibrillary tangle accumulation. Vervets in the trial fed smaller doses of BMAA were found to have correlative decreases in these pathology features. This study demonstrates that BMAA, an environmental toxin, can trigger neurodegenerative disease as a result of a gene/environment interaction. While BMAA has been detected in brain tissue of deceased ALS/PDC patients, further insight is required to trace neurodegenerative pathology in humans to BMAA.

History

Pathophysiology

Exogenous excitotoxins

BMAA

See also

References

Further reading