Abstract
Neurodegenerative diseases are collective diseases that affect different parts of the brain with common or distinct disease phenotype. In almost all of the Prion diseases, motor impairments that are characterized by motor derangement, apathy, ataxia, and myoclonus are documented and again are shared by motor neuron diseases (MND). Proteins such as; B-Cell lymphoma 2 (BCL2), Copper chaperone for superoxide dismutase (CCS), Amyloid beta precursor protein (APP), Amyloid Precursor-Like Protein1/2 (APLP1/2), Catalase (CAT), and Stress induced phosphoprotein 1 (STIP1), are common interactomes of Prion and superoxide dismutase 1 (SOD1). Although there is no strong evidence to show the interaction of SOD1 and Prion, the implicated common interacting proteins indicate the potential bilateral interaction of those proteins in health and disease. For example, down-regulation of Heat shock protein A (HSPA5), a Prion interactome, increases accumulation of misfolded SOD1 leading to MND. Loss of Cu uptake function disturbs normal function of CCS. Over-expressed proteasome subunit alpha 3 (PSMA3) could fatigue its normal function of removing misfolded proteins. Studies showed the increase in CAT and lipid oxidation both in Prion-knocked out animal and in catalase deficiency cases. Up regulation, down regulation or direct interaction with their interactomes are predicted molecular mechanisms by which Prion and SOD exert their effect. The loss of protective function or the gain of a novel toxic property by the principal proteins is shared in Prion and MND. Thus, it might be possible to conclude that the interplay of proteins displayed in both diseases could be a key phenomenon in motor dysfunction development.
Highlights
Neurodegenerative disease is a global concern and poses serious social and individual challenges
Proteins such as; B-Cell lymphoma 2 (BCL2), Copper chaperone for superoxide dismutase (CCS), Amyloid beta precursor protein (APP), Amyloid Precursor-Like Protein1/2 (APLP1/2), Catalase (CAT), and Stress induced phosphoprotein 1 (STIP1), are common interactomes of Prion and superoxide dismutase 1 (SOD1)
B-Cell lymphoma 2 (BCL2) [80] [81], Smith-Magenis syndrome chromosome region, candidate 8 (SMCR8), Proteasome subunit alpha 3 (PSMA3), Copper chaperone for superoxide dismutase (CCS) [82], Amyloid beta precursor protein (APP) [83] [84], Amyloid Precursor-Like Protein (1APLP1/2) [85], WD repeat domain (5WDR5), Homeobox (A1HOXA1) [86], and Catalase (CAT) [87] are identified to interact with Prion with a variety of cellular function
Summary
Neurodegenerative disease is a global concern and poses serious social and individual challenges. Apart from those, Prion diseases are characterized as the lethal form of neurodegenerative diseases with no clearly defined molecular mechanism and cure. The basis for the predicative pathomechanism is the absence of evidence of definite physiologic function of cellular Prion [4] [5] [6] [7]. There is presumption that the normal physiologic function of cellular Prion depends on other proteins that interact with it [8] [12]. Some of the clinical features that are implicated in Prion diseases might be because of the same molecular phenomena of other diseases which are explained by up-regulation, down-regulation or abnormal interaction with the specific protein
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