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Dulski, J.

Publications and source records attributed to Dulski, J..

2 recordsLinked to original sources
bioRxiv2025

Overview of non-coding RNAs with CAG repeats and the case of mutation-containing circRNA in polyglutamine disease patients

CAG trinucleotide repeats are present in protein-coding and non-coding RNAs (ncRNAs). They are polymorphic in length and can cause neurodegenerative diseases when expanded, e.g., spinocerebellar ataxia type 7 (SCA7) is caused by a mutation in the ATXN7 gene. We focused on RNAs with at least 10 CAG repeats and identified several hundred mRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) originating from 49 genomic loci. These loci differ in the rate of length polymorphism in the population, and some of the tracts show an interesting pattern of adjacent CAA triplet, as well as present variable interruption profiles. For ATXN7 locus, we investigated two circRNAs for which we confirmed the expression in the human brain, SCA7 fibroblasts and blood samples. Moreover, we report an intriguing example of circRNA containing a mutant CAG tract, experimentally validated in SCA7 patients.

molecular biology↗
bioRxiv2025

Targeted plasma proteomics uncover novel proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders

KIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a novel multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10, ALS patients and compared to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function, and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG10 patients. Moreover, these findings can now be taken forward to gain mechanistic understanding of axonopathies linking to N-vs C-terminal KIF5A variants affecting both central and peripheral nervous systems.

neuroscience↗