Role of Extracellular Matrix in Neurodevelopment and Neurodegeneration

About this Research Topic

Background

Extracellular matrix (ECM) is the non-cellular component of the nervous system which provides both physical support and signaling regulation. Brain ECM is unique both in function and composition. Various cells of the nervous system including neurons and glial cells contribute to the ECM, which comprises a hyaluronan backbone with attached chondroitin sulfate proteoglycans (CSPGs) of the lectican family, along with tenascins. The composition of the ECM differs through various stages of development signifying its diverse and evolving functions in regulating cell differentiation, migration, axonal outgrowth, synaptic connectivity, and neural health. It serves as a reservoir of various secretory factors that shape the tissue remodeling and morphogenesis.

During development, an ECM component can have multiple, even opposing, roles and can affect neural cells in diverse ways. Adding further complexity, cells can alter their own ECM environment very quickly, either by changing the expression of ECM components or by producing enzymes that degrade the ECM. The ECM has also emerged as an important regulator of synaptic plasticity through its two specialized types, namely the diffuse perisynaptic ECM and the condensed ECM which surrounds the initial part of dendritic trees in specialized neuron subtypes forming the perineuronal nets (PNNs). In relevance to their critical role regulation of developmental spine remodeling, malleability during learning and memory, regulation of synaptic plasticity and receptor trafficking, perineuronal nets are the most extensively studied, opening up several interesting questions.
Neurodegenerative diseases like, Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) result from gradual and progressive loss of neural cells and changes in ECM components that lead to brain dysfunction. ECM adhesion is critical for cell survival, therefore, it is not surprising that ECM has been increasingly found to be associated with neurodegenerative diseases. Heparan sulfates regulate the amyloid precursor protein cleavage, biasing it towards amyloidogenic pathways resulting in Alzheimer’s disease. Several heparan sulfate proteoglyans, including syndecan, glypican, and agrin can be detected in amyloid plaques. Recently the ECM structural components including collagens, proteoglycans and glycosaminoglycan binding molecules were also found to be upregulated in Parkinson's disease compared to age matched controls. So far, the majority of neuroscience research has been focused on the cellular components of neurodevelopment and degeneration, however the molecular significance and the mechanisms regulating the dynamic nature of ECM composition are still far from clear.

Therefore, the role of extracellular system on the etiology and progression of nervous system pathologies remains largely underexplored. There is an urgent need to develop sophisticated tools and techniques, including easy to interpret in vitro and in vivo model systems to decipher the complex composition, functions and regulation of the ECM at various stages of neurodevelopment and how they are remodeled in neurodegenerative conditions.
This Research Topic aims to create a multidisciplinary collection of recent advances on the ECM in neurodevelopment and degenerative diseases. We welcome authors to contribute Original Research, Review, Mini-Review, Hypothesis and Theory, Perspective, Clinical Trial, Case Report and Opinion articles that cover, but are not limited to, the following topics that will represent current knowledge and stimulate investigation on the ECM and its implications in the psychiatric and neurodegenerative disorders.

● Role of ECM in cell adhesion and its implications in neurodegenerative disorders
● Role of ECM in maturation and function of cytoskeletal structures like filopodia in tissue remodeling during early neurodevelopment
● Role of extracellular proteins including but not limited to Integrins, semaphorins, and reelin on the ECM. and implications in neurological diseases.
● Importance of Chondroitin sulfate proteoglycans in dendritic spine morphogenesis. and implications in neurodegenerative conditions and psychiatric disorders like schizophrenia.
● How PNNs regulate the closure of critical periods of heightened neuroplasticity. implications in a range of neurodegenerative and neuropsychiatric disorders.
● Tools and techniques for investigation of ECM components, their regulation and function.

Integration of the thought-provoking knowledge compiled in these articles will lead to better understanding of the composition, and regulation of the ECM in neural development, functions and degeneration as well as lead to potential new therapeutic strategies in future.

Keywords: Neurodevelopment, Perineuronal Nets, Extracellular matrix, Chondroitin sulfate proteoglycans, Neurodegeneration, Psychiatric disorders

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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