Nucleic Acid Therapies for Ischemic Stroke

Abstract

Stroke remains a leading cause of disability and death worldwide despite significant scientific and therapeutic advances. Therefore, there is a critical need to improve stroke prevention and treatment. In this review, we describe several examples that leverage nucleic acid therapeutics to improve stroke care through prevention, acute treatment, and recovery. Aptamer systems are under development to increase the safety and efficacy of antithrombotic and thrombolytic treatment, which represent the mainstay of medical stroke therapy. Antisense oligonucleotide therapy has shown some promise in treating stroke causes that are genetically determined and resistant to classic prevention approaches such as elevated lipoprotein (a) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Targeting microRNAs may be attractive because they regulate factors involved in neuronal cell death and reperfusion-associated injury, as well as neurorestorative pathways. Lastly, microRNAs may aid reliable etiologic classification of stroke subtypes, which is important for effective secondary stroke prevention.

Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms

“…Moreover, the ACAP3 gene, in which UPS29 is located, may play a role in the development of this disease and other neurological pathologies under environmental influences. The structural and epigenetic changes of intra-intronic minisatellite observed in this work upon epilepsy and perhaps for other neurological disease points to possible usage of nucleic acid (in particular non-coding tandem repeats) therapies as was suggested in [108][109][110]. All these statements concerning the molecular mechanisms of action of UPS29 and ACAP3 in the etiopathogenesis of epilepsy require further research.…”

Principles and requirements for stroke recovery science

“…One of the advantages of this method is a multifaceted impact on all components of the regenerative machinery. 27 , 28 The decryption of the epigenetic regulation thus potentially allowing epigenetic reprogramming of the genetic machinery including regeneration enhancers will become a major task for the next years and decades to potentially do a significant step towards successful regenerative therapy of stroke-damaged tissue (for overview, see Ref. 29 ).…”

Detrimental and Beneficial Effect of Autophagy and a Potential Therapeutic Target after Ischemic Stroke

“…MicroRNAs (miRNAs) are composed of 20–25 endogenous, noncoding, single-stranded RNA molecules. They regulate target genes' expressions and can modulate cell proliferation, differentiation, apoptosis, and metabolism [ 101 ]. Recent studies suggest that cerebral ischemia leads to abnormal changes in miRNA expression levels, which are involved in the etiology and pathology of sequelae after stroke.…”