Proteomic analysis of opossum Monodelphis domestica spinal cord reveals the changes of proteins related to neurodegenerative diseases during developmental period when neuroregeneration stops being possible

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

“…Understanding why neuroregeneration fails in the adult mammalian CNS would give the possibility to alter the key pathways to promote cell survival and axon regeneration and possibly alter the outcome of neurodegenerative diseases, including ALS [ 80 ]. The comprehensive analysis of the proteins that change during the early developmental period when neuroregeneration in CNS stops being possible revealed the abundance of the proteins related to neurodegenerative diseases, including the proteins coded by the genes related to the ALS risk loci [ 17 ]. Those results connect ALS with neurodevelopment and neuroregeneration, with the possible identification of new diagnostic and therapeutic targets.…”

“…In previous studies [ 87 , 88 ], differentially expressed genes were identified in opossum spinal cords during the critical period of development when regeneration stops being possible, revealing the molecules involved in nucleic acid management, protein synthesis and processing, the control of cell growth, structure and motility, cell signaling, extracellular matrix molecules, and their receptors. The transcriptomic data were upgraded with proteomic research [ 17 ], to select the overlapping molecules as the most promising candidates controlling regeneration, to be tested in functional studies.…”

“…Among the proteins that are differentially distributed in opossum spinal tissue that can and cannot regenerate after injury, we identified the numerous proteins related to neurodegenerative diseases, such as Huntington’s, Parkinson’s, and Alzheimer’s disease [ 17 ]. Interestingly, the ALS-related proteins were detected, among which were those connected to the 15 risk loci linked to ALS [ 16 ] ( Table 2 ).…”

“…Common ALS-related genes/proteins identified in [ 16 ] ( Table 1 ) and in the proteome analysis of developing opossum spinal cord [ 17 ] ( Table 2 ) are summarized in Figure 2 . It is still to be tested if the ALS-related genes/proteins have an impact on neuronal regeneration.…”

“…Both the diagnosis and treatment of the disease are currently insufficient, primarily due to deficient knowledge of genetic and molecular causes of the disease as well as pathological pathways involved in the disease progression. Here, we propose a possible connection of ALS with neuroregeneration and aberrant early central nervous system (CNS) development [ 16 , 17 ], where the complex pathophysiology could be orchestrated by several non-coding RNAs that also could present potentially useful biomarkers in ALS prognosis and diagnosis. Moreover, the miRNA and lncRNA molecules known to control the expression of the ALS-related genes of interest have been co-located both in the peripheral blood of ALS patients, as well as in brain and spinal cord tissues [ 18 , 19 ], giving a strong indication of possible involvement and importance in the control of both CNS development and ALS pathophysiology.…”