Publications

The extracellular matrix (ECM) is a dynamic and complex network of proteins and molecules that surrounds cells and tissues in the nervous system and orchestrates a myriad of biological functions. This review carefully examines the diverse interactions between cells and the ECM, as well as the transformative chemical and physical changes that the ECM undergoes during neural development, aging, and disease. These transformations play a pivotal role in shaping tissue morphogenesis and neural activity, thereby influencing the functionality of the central nervous system (CNS). In our comprehensive review, we describe the diverse behaviors of the CNS ECM in different physiological and pathological scenarios and explore the unique properties that make ECM-based strategies attractive for CNS repair and regeneration. Addressing the challenges of scalability, variability, and integration with host tissues, we review how advanced natural, synthetic, and combinatorial matrix approaches enhance biocompatibility, mechanical properties, and functional recovery. Overall, this review highlights the potential of decellularized ECM as a powerful tool for CNS modeling and regenerative purposes and sets the stage for future research in this exciting field. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants

JTD Keywords: Amyotrophic-lateral-sclerosis, Biologic scaffold, Central nervous system, Central-nervous-system, Chondroitin sulfate proteoglycans, Decellularization, Extracellular matrix, Motor-neurons, Neural disorders, Neural regeneratio, Perineuronal nets, Self-healing hydrogel, Spinal-cord-injury, Stem-cell, Vascular basement-membrane

Proprioceptive sensory neurons (pSN) are an essential and undervalued part of the neuromuscular circuit. A protocol to differentiate healthy and amyotrophic lateral sclerosis (ALS) human neural stem cells (hNSC) into pSN, and their comparison with the motor neuron (MN) differentiation process from the same hNSC sources, facilitated the development of in vitro co-culture platforms. The obtained pSN spheroids cultured interact with human skeletal myocytes showing the formation of annulospiral wrapping-like structures between TrkC + neurons and a multinucleated muscle fibre, presenting synaptic bouton-like structures in the contact point. The comparative analysis of the genetic profile performed in healthy and sporadic ALS hNSC differentiated to pSN suggested that basal levels of ETV1, critical for motor feedback from pSN, were much lower for ALS samples and that the differences between healthy and ALS samples, suggest the involvement of pSN in ALS pathology development and progression.© 2022. The Author(s).

JTD Keywords: Amyotrophic-lateral-sclerosis,pluripotent stem-cells,peripheral nervous-system,stretch reflex arc,mechanosensory circuit,cellular-localization,molecular-cloning,motor-neurons,muscle,expressio

Many neurodegenerative disorders display protein aggregation as a hallmark, Huntingtin and TDP-43 aggregates being characteristic of Huntington disease and amyotrophic lateral sclerosis, respectively. However, whether these aggregates cause the diseases, are secondary by-products, or even have protective effects, is a matter of debate. Mutations in both human proteins can modulate the structure, number and type of aggregates, as well as their toxicity. To study the role of protein aggregates in cellular fitness, we have expressed in a highly tractable unicellular model different variants of Huntingtin and TDP-43. They each display specific patterns of aggregation and toxicity, even though in both cases proteins have to be very highly expressed to affect cell fitness. The aggregation properties of Huntingtin, but not of TDP-43, are affected by chaperones such as Hsp104 and the Hsp40 couple Mas5, suggesting that the TDP-43, but not Huntingtin, derivatives have intrinsic aggregation propensity. Importantly, expression of the aggregating form of Huntingtin causes a significant extension of fission yeast lifespan, probably as a consequence of kidnapping chaperones required for maintaining stress responses off. Our study demonstrates that in general these prion-like proteins do not cause toxicity under normal conditions, and in fact they can protect cells through indirect mechanisms which up-regulate cellular defense pathways. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

JTD Keywords: aggregation, antioxidant, degradation, features, fission yeast, gene, huntingtin, neurodegenerative diseases, pap1, polyglutamine toxicity, protein aggregation, proteins, stress, tdp-43, Amyotrophic-lateral-sclerosis, Chaperone, Chemistry, Dna binding protein, Dna-binding proteins, Fission yeast, Genetics, Human, Humans, Huntingtin, Metabolism, Molecular chaperones, Neurodegenerative diseases, Prion, Prions, Protein aggregate, Protein aggregates, Protein aggregation, Schizosaccharomyces, Tdp-43