The Spatiotemporal Coupling: Regional Energy Failure and Aberrant Proteins in Neurodegenerative Diseases

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 11304
• Main Authors: Virtuoso, Assunta, Colangelo, Anna Maria, Maggio, Nicola, Fennig, Uri, Weinberg, Nitai, Papa, Michele, De Luca, Ciro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.10.2021; MDPI
• Subjects: Alzheimer's disease; Animals; Astrocytes - metabolism; Biomarkers; Brain; Central nervous system; Central Nervous System - metabolism; Central Nervous System - physiopathology; Energy consumption; extra-cellular matrix; Extracellular matrix; Functional anatomy; Gene expression; Heparan sulfate; Humans; Immune system; Metabolism; Microglia - metabolism; Neurodegeneration; neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neuroglia - metabolism; Neurological diseases; Neuronal Plasticity - physiology; Neurons - metabolism; neurovascular unit; Parkinson's disease; Pathology; Phenotypes; Phosphorylation; Proteins; Review; Spatio-Temporal Analysis; Synapses - metabolism; Synaptic cleft; Synaptic plasticity; systems biology; systems biology; neurodegenerative diseases; extra-cellular matrix; metabolism; astrocytes; synaptic plasticity; microglia; neurons; neurovascular unit; oligodendroglia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111304

The spatial and temporal coordination of each element is a pivotal characteristic of systems, and the central nervous system (CNS) is not an exception. Glial elements and the vascular interface have been considered more recently, together with the extracellular matrix and the immune system. However, the knowledge of the single-element configuration is not sufficient to predict physiological or pathological long-lasting changes. Ionic currents, complex molecular cascades, genomic rearrangement, and the regional energy demand can be different even in neighboring cells of the same phenotype, and their differential expression could explain the region-specific progression of the most studied neurodegenerative diseases. We here reviewed the main nodes and edges of the system, which could be studied to develop a comprehensive knowledge of CNS plasticity from the neurovascular unit to the synaptic cleft. The future goal is to redefine the modeling of synaptic plasticity and achieve a better understanding of neurological diseases, pointing out cellular, subcellular, and molecular components that couple in specific neuroanatomical and functional regions.