A synaptopathy is a disease of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

relating to the dysfunction of synapses. This can arise as a result of a mutation in a gene encoding a synaptic protein such as an ion channel, neurotransmitter receptor, or a protein involved in

neurotransmitter release Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use ...

. It can also arise as a result of an

autoantibody An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. P ...

targeting a synaptic protein. Synaptopathies caused by ion channel mutations are also known as synaptic

channelopathies Channelopathies are a group of diseases caused by the dysfunction of ion channel subunits or their interacting proteins. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in genes encoding ion channels, wh ...

. An example is

episodic ataxia Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recog ...

. Myasthenia gravis is an example of an

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...

synaptopathy. Some toxins also affect synaptic function.

Tetanus toxin Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of ''Clostridium tetani'' in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally ...

and botulinum toxin affect neurotransmitter release. Tetanus toxin can enter the body via a wound, and botulinum toxin can be ingested or administered therapeutically to alleviate dystonia or as cosmetic treatment. Another example of synaptopathy occurs in the auditory system. This cochlear synaptopathy has been seen after prolonged noise exposure in both primate and non-primate models. Two possible reasons for this neuronal death are both glutamate-mediated

excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate ...

in the postsynaptic terminal, and presynaptic ribbon damage which occurs by an unknown mechanism. Synaptopathies are attracting research interest because they provide an insight into fundamental mechanisms of synaptic transmission and because an improved understanding of disease mechanisms may lead to new treatments. Some diseases of unknown etiology have been proposed to be synaptopathies. Examples include

autism spectrum disorder The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

and

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

. Synaptic dysfunction can also occur in

neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

disorders such as Alzheimer's. Immune-mediated cerebellar ataxias represent a group of disorders causing cerebellar ataxia induced by a dysfunction of synapses. Increasing knowledge of the genetic basis of these diseases has linked proteins to the function of the synapse. Age-related cochlear synaptic and neural degeneration has also been demonstrated in mice. Molecules such as FMRP1 act as translational repressor thus when ablated such as in FXS result in varying degrees of cellular and behavioural abnormalities. Additional molecules thought to be involved include SynGAP and

SHANK1 SH3 and multiple ankyrin repeat domains protein 1 is a protein that in humans is encoded by the ''SHANK1'' gene. Interactions SHANK1 has been shown to interact with: * ARHGEF7, * BAIAP2, * DNM2, * SPTAN1 Alpha II-spectrin, also known as S ...

References

{{Reflist

External links

* https://www.ucl.ac.uk/ion/synaptopathies Neurological disorders