RNA TRANSLATION IN NEURODEGENERATIVE DISORDERS AN UPDATE ON THE BIOLOGY, AND CELLULAR MECHANISMS

Secondary structures like hairpins, stem loops, and pseudoknots modify the ribosomes' binding, scanning, and recognition of start codons and control the levels of protein expression. These structures can affect translation start depending on their position. Research indicates that somatic and germline mutations, as well as a number of neurological disorders are caused due to these secondary structures. Repeat-associated non-AUG (RAN) translation, which generates dipeptide repeat proteins (DPRs), is the most prevalent genetic cause of several neurological disorders. Model species like yeast, Drosophila, cultured cells, and primary mammalian neurons have provided insights into Biological, cellular and pathological aspects of DRP. Cumulatively, the research indicates reduced cell death and/or survival. Bidirectional transcription in repeat regions of genes associated with several human neurological disorders has been documented. The identification of new proteins accumulating in the relevant tissues of the illnesses in both patients and model organisms suggest that homopolymeric or dipeptide repeat are associated non-AUG (RAN) translation. Spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome, C9ORF72 amyotrophic lateral sclerosis, and frontotemporal dementia are few disorders associated are the disorders associated. Recently, there has been a lot of interest in using antisense oligonucleotides (ASOs) to treat the pathology. Thus this area of non-canonical translation and protein toxicity has importance both from basic science and disease perspectives. The current review is an update on the topic covering diverse areas by providing the necessary background.