The Potential Connection between Molecular Changes and Biomarkers Related to ALS and the Development and Regeneration of CNS

Abstract

Neurodegenerative diseases are one of the greatest medical burdens of the modern age, being mostly incurable and with limited prognostic and diagnostic tools. Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the loss of motoneurons, with a complex etiology, combining genetic, epigenetic, and environmental causes. The neuroprotective therapeutic approaches are very limited, while the diagnostics rely on clinical examination and the exclusion of other diseases. The recent advancement in the discovery of molecular pathways and gene mutations involved in ALS has deepened the understanding of the disease pathology and opened the possibility for new treatments and diagnostic procedures. Recently, 15 risk loci with distinct genetic architectures and neuron-specific biology were identified as linked to ALS through common and rare variant association analyses. Interestingly, the quantity of related proteins to these genes has been found to change during early postnatal development in mammalian spinal cord tissue (opossum Monodelphis domestica) at the particular time when neuroregeneration stops being possible. Here, we discuss the possibility that the ALS-related genes/proteins could be connected to neuroregeneration and development. Moreover, since the regulation of gene expression in developmental checkpoints is frequently regulated by non-coding RNAs, we propose that studying the changes in the composition and quantity of non-coding RNA molecules, both in ALS patients and in the developing central nervous (CNS) system of the opossum at the time when neuroregeneration ceases, could reveal potential biomarkers useful in ALS prognosis and diagnosis.

Diffusion magnetic resonance imaging-based surrogate marker in amyotrophic lateral sclerosis

“…It is quite probable that the most significant barrier that stands in the way of reducing this amount of time is a basic lack of understanding about the greater group of individuals who are at risk of developing ALS. It is possible that a higher understanding among primary care doctors and other medical professionals who are not neurologists might be of some value in lowering the amount of time it takes to diagnose [20][21][22]. This diagnosis delay highlights the lack of clearly identifiable surrogate markers that are currently available in ALS.…”

Label-Free Long-Term Methods for Live Cell Imaging of Neurons: New Opportunities

“…Moreover, the mature mammalian CNS neurons (unlike the peripheral neurons and the CNS of lower vertebrates) fail to (fully) regenerate following injury, and the exact reasons and advantages for this evolutionary choice in turning off regeneration and plasticity in the adult mammals are still poorly understood [ 11 , 12 , 13 , 14 ]. A full description of the molecular mechanisms that occur during development and maturation of such a complex system is fundamental for designing effective therapies for neurodegenerative diseases, since many common developmental pathways, including cell cycle machinery, are found to be misexpressed in Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) patients [ 2 , 10 , 15 , 16 ].…”