Integrin Signaling in the Central Nervous System in Animals and Human Brain Diseases

Abstract

The integrin family is involved in various biological functions, including cell proliferation, differentiation and migration, and also in the pathogenesis of disease. Integrins are multifunctional receptors that exist as heterodimers composed of α and β subunits and bind to various ligands, including extracellular matrix (ECM) proteins; they are found in many animals, not only vertebrates (e.g., mouse, rat, and teleost fish), but also invertebrates (e.g., planarian flatworm, fruit fly, nematodes, and cephalopods), which are used for research on genetics and social behaviors or as models for human diseases. In the present paper, we describe the results of a phylogenetic tree analysis of the integrin family among these species. We summarize integrin signaling in teleost fish, which serves as an excellent model for the study of regenerative systems and possesses the ability for replacing missing tissues, especially in the central nervous system, which has not been demonstrated in mammals. In addition, functions of astrocytes and reactive astrocytes, which contain neuroprotective subpopulations that act in concert with the ECM proteins tenascin C and osteopontin via integrin are also reviewed. Drug development research using integrin as a therapeutic target could result in breakthroughs for the treatment of neurodegenerative diseases and brain injury in mammals.

Keywords: CNS; astrocyte; axon; invertebrate; mammal; mouse; neuron; phylogenetic tree; regeneration; teleost fish.

Figure 2

Involvement of integrins in CNS regeneration in collaboration with potential factors. Modulation of integrins with potential factor(s) stated in the main text, and possibly also the environment, could convert astrocytes or reactive astrocytes to healthy neurons for induction of neuro-regeneration in the mammalian CNS. The number(s) in square brackets beside the factor names are the reference numbers cited in the main text [28,29,30,31,84,87,106,107,108,109,112,114].

Figure 1

Phylogenetic relationship of PS4 integrin group. Protein sequences of the vertebrate integrins α4 and α9 and invertebrate integrins (α ina-1 and pat-2 of Caenorhabditis elegans, α4 of Octopus sinensis, αPS4 of Drosophila melanogaster, and α int-4 of Schmidtea mediterranea) obtained from the NCBI were aligned using the ClustalW algorithm, and a phylogenetic tree was drawn with Neighbor-Joining on MEGA11 [33].