The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer's and Parkinson's Diseases.

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.

Widespread occurrence and diverse origins of polintoviruses influence lineage-specific genome dynamics in stony corals.

Stony corals (Order: Scleractinia) are central to vital marine habitats known as coral reefs. Numerous stressors in the Anthropocene are contributing to the ongoing decline in coral reef health and coverage. While viruses are established modulators of marine microbial dynamics, their interactions within the coral holobiont and impact on coral health and physiology remain unclear. To address this key knowledge gap, we investigated diverse stony coral genomes for 'endogenous' viruses. Our study uncovered a remarkable number of integrated viral elements recognized as 'Polintoviruses' (Class Polintoviricetes) in thirty Scleractinia genomes; with several species harboring hundreds to thousands of polintoviruses. We reveal massive paralogous expansion of polintoviruses in stony coral genomes, alongside the presence of integrated elements closely related to Polinton-like viruses (PLVs), a group of viruses that exist as free virions. These results suggest multiple integrations of polintoviruses and PLV-relatives, along with paralogous expansions, shaped stony coral genomes. Re-analysis of existing gene expression data reveals all polintovirus structural and non-structural hallmark genes are expressed, providing support for free virion production from polintoviruses. Our results, revealing a significant diversity of polintovirus across the Scleractinia order, open a new research avenue into polintovirus and their possible roles in disease, genomic plasticity, and environmental adaptation in this key group of organisms.

A Novel TTC19 Mutation in a Patient With Neurological, Psychological, and Gastrointestinal Impairment.

Mitochondrial complex III deficiency nuclear type 2 is an autosomal-recessive disorder caused by mutations in TTC19 gene. TTC19 is involved in the preservation of mitochondrial complex III, which is responsible for transfer of electrons from reduced coenzyme Q to cytochrome C and thus, contributes to the formation of electrochemical potential and subsequent ATP generation. Mutations in TTC19 have been found to be associated with a wide range of neurological and psychological manifestations. Herein, we report on a 15-year-old boy born from first-degree cousin parents, who initially presented with psychiatric symptoms. He subsequently developed progressive ataxia, spastic paraparesis with involvement of caudate bodies and lentiform nuclei with cerebellar atrophy. Eventually, the patient developed gastrointestinal involvement. Using whole-exome sequencing (WES), we identified a novel homozygous frameshift mutation in the TTC19 gene in the patient (NM_017775.3, c.581delG: p.Arg194Asnfs*16). Advanced genetic sequencing technologies developed in recent years have not only facilitated identification of novel disease genes, but also allowed revelations about novel phenotypes associated with mutations in the genes already linked with other clinical features. Our findings expanded the clinical features of TTC19 mutation to potentially include gastrointestinal involvement. Further functional studies are needed to elucidate the underlying pathophysiological mechanisms.