Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

enzyme that in humans is encoded by the ''PNPLA6''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. Neuropathy target esterase is a

phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step i ...

that deacetylates intracellular

phosphatidylcholine Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup. They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or so ...

to produce

glycerophosphocholine L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound found in the brain. It is also a parasympathomimetic acetylcholine precursor which has been investigated for its potential for the treatment of Alzh ...

. It is thought to function in

neurite outgrowth A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in cultur ...

and process elongation during

neuronal differentiation A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

. The protein is anchored to the cytoplasmic face of the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

in both neurons and non-neuronal cells.

Function

Neuropathy target esterase is an enzyme with

phospholipase B Phospholipase B, also known as lysophospholipase, is an enzyme with a combination of both PLA1 and PLA2 activities; that is, it can cleave acyl chains from both the sn-1 and sn-2 positions of a phospholipid. In general, it acts on lysolecithin (wh ...

activity: it sequentially hydrolyses both fatty acids from the major membrane lipid

, generating water-soluble glycerophosphocholine. In

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...

cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In mammals, it is particularly abundant in neurons, the

placenta The placenta is a temporary embryonic and later fetal organ (anatomy), organ that begins embryonic development, developing from the blastocyst shortly after implantation (embryology), implantation. It plays critical roles in facilitating nutrien ...

, and the kidney. Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the

constitutive secretory pathway Constitutive may refer to: * In physics, a constitutive equation is a relation between two physical quantities * In ecology, a constitutive defense is one that is always active, as opposed to an inducible defense * Constitutive theory of statehood ...

in neurons. In the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

, the expression of neuropathy target esterase is regulated by TonEBP as part of

osmolyte Osmolytes are low-molecular weight organic compounds that influence the properties of biological fluids. Their primary role is to maintain the integrity of cells by affecting the viscosity, melting point, and ionic strength of the aqueous solution. ...

production when the kidney produces concentrated

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

Clinical significance

Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents. Recessively-inherited mutations in ''NTE'' that substantially reduce its catalytic activity cause a rare form of

hereditary spastic paraplegia Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditar ...

(SPG39), in which distal parts of long spinal

axons An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

degenerate leading to limb weakness and paralysis.

Organophosphate-induced delayed neuropathy Organophosphate-induced delayed neuropathy (OPIDN), also called organophosphate-induced delayed polyneuropathy (OPIDP), is a neuropathy caused by killing of neurons in the central nervous system, especially in the spinal cord, as a result of acute ...

a paralysing syndrome with distal degeneration of long axons results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.

Function

Clinical significance

References

Further reading