In biology, fractones are structures consisting primarily of laminin and

heparan sulfate proteoglycan Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

(HSPG) first discovered in the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

niche of the

subventricular zone The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...

of the lateral ventricle (SVZa) in the mouse brain. Recent research has suggested its importance in adult neurogenesis,

gliogenesis Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells. Overview Gliogenesis results in the formation of non-neuronal glia populations from neuronal cells. In this capacity, glial cells provide m ...

, and

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

. Fractones are found near or connected to

stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

, and are highly implicated in cell proliferation, differentiation and migration. New work suggests that fractones are implicated in corticalization during embryogenesis, as well as in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and

neurodegenerative disease 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 ...

History

The term ''fractone'' is derived from

fractal In mathematics, a fractal is a geometric shape containing detailed structure at arbitrarily small scales, usually having a fractal dimension strictly exceeding the topological dimension. Many fractals appear similar at various scales, as illu ...

, a term coined by

Benoît Mandelbrot Benoit B. Mandelbrot (20 November 1924 – 14 October 2010) was a Polish-born French-American mathematician and polymath with broad interests in the practical sciences, especially regarding what he labeled as "the art of roughness" of phy ...

in 1975. Fractones were discovered in 2002 in the

niche of the

of the lateral ventricule (SVZa) in a mouse brain. Originally found in the neurogenic areas of the brain, recent studies indicate that fractones are also present in multiple organisms, including but not limited to

plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

s, and

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

animals. As the discovery of fractones marked a turning point in neurosciences and the understanding of stem cell niches in the mammal brain, other projects have been conducted in different organs and Fractones were found to be highly implicated not only in physiology but also in numerous pathologies. For instance, fractones are extremely reduced in

Autism 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 ...

but highly represented in inflammation, cancer and other pathologies.

Properties

Fractones are structures composed of proteoglycans, consisting primarily but not limited to laminin and HSPG. Different patterns of sulfation in HSPG and chain length are responsible for numerous pathways in physiology as well as in pathology, being involved in most

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...

bindings, and in

embryo development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, s ...

, cancer, and other pathologies. The HSPG part of fractones is responsible for

binding, retention and release in the

. Moreover, fractones are always linked to cell processes, thus connecting up to 20 different cells to a single fractone, acting as a control panel for all of them.

Physiology

Fractones are

structures first discovered in the neurogenic zone of the brain. Fractones primarily consist of

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...

s such as laminin and HSPG. These proteoglycans bind

in the extracellular matrix to regulate stem cell proliferation, which has been demonstrated in the adult brain neurogenic zone, where fractones are responsible for the ''production'' and ''differenciation'' of new neurons. The main role of these structures, linked to a wide array of cells, is to act as a control panel for cell proliferation, differentiation and migration. Fractones also regulate stem cell fate in the brain, ''controlling'' how a stem cell should evolve.

Embryonic development

Fractones have been described in the early development of the mouse embryo as punctates of laminin and/or HSPG. They adopt different patterns at each stage of the development, from the 2-cell stage to post-natal stages. Recent studies laso show that fractones play a key role in corticalization and the establishment of the subventricular zone and the ventricular zone of the lateral ventricule

Cancer

Recent work suggests that fractones are omnipresent in cancer. As fractones are believed to be either pre- or post-

basement membrane The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...

structures, analysis of fractone-markers in patients with

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

, intestine and stomach carcinoma, kidney, liver, lung and ovary tumors revealed numerous fractones while basement membranes were usually absent. This may indicates changes in the

tumor microenvironment The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are cl ...

that may rewire cancerous cells and promote growth and proliferation.

Alzheimer's disease

Fractones might have also already been described in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

(AD) as they are depicted as laminin and/or HSPG punctates.

Amyloid plaque Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of micr ...

-associated punctates of laminin and

have already been described in several sources, but not yet associated with fractone research.

References

{{reflist Neuroscience