Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey.

By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aß aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.

Mitochondrial dynamics related neurovascular approaches in cerebral ischemic injury.

Mitochondria are double-membrane organelles that provide the majority of a cell's energy. Furthermore, mitochondria are involved in various cellular biological activities, including calcium signalling, reactive oxygen species production, apoptosis, cell development, and the cell cycle. Mitochondrial dysfunction is seen in various neurological conditions involving acute and chronic neural injury, including neurodegenerative diseases, hypoxia-induced brain injury, and ischemia. This review made a significant contribution to the explanation of the idea that mitochondria would both be critical targets of ischemia-induced processes, including intracellular calcium elevation and reactive oxygen species and essential sites for determining cell viability loss. As a result, it's not unexpected that attempts to prevent I/R damage have focused on mitochondria. Drugs such as vatiquinone, vitexin, dexprmipexole, baicalin, nobiletin, via promoting mitochondrial activities, can be used in future studies for protecting the brain from ischemia injury. This review summarizes mitochondrial pathways, i.e., Bad, Drp-1, JNK/caspase-3, MAPK-ERK, p53, Wnt/ß-Catenin, that contribute to disease progression. We have précised the potential regulatory role of miRNA-mitochondrial dynamics in cerebral ischemic-reperfusion injury and associated molecular mechanisms; also provide insight into the potential therapies for cerebral injury-induced injuries.

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends.

AIMS: The novel Coronavirus disease 2019 (COVID-19) has caused great distress worldwide. Acute respiratory distress syndrome (ARDS) is well familiar but when it happens as part of COVID-19 it has discrete features which are unmanageable. Numerous pharmacological treatments have been evaluated in clinical trials to control the clinical effects of CARDS, but there is no assurance of their effectiveness. MATERIALS AND METHODS: A systematic review of the literature of the Medline, Scopus, Bentham, PubMed, and EMBASE (Elsevier) databases was examined to understand the novel therapeutic approaches used in COVID-19-Associated Acute Respiratory Distress Syndrome and their outcomes. KEY FINDINGS: Current therapeutic options may not be enough to manage COVID-19-associated ARDS complications in group of patients and therefore, the current review has discussed the pathophysiological mechanism of COVID-19-associated ARDS, potential pharmacological treatment and the emerging molecular drug targets. SIGNIFICANCE: The rationale of this review is to talk about the pathophysiology of CARDS, potential pharmacological treatment and the emerging molecular drug targets. Currently accessible treatment focuses on modulating immune responses, rendering antiviral effects, anti-thrombosis or anti-coagulant effects. It is expected that considerable number of studies conducting globally may help to discover effective therapies to decrease mortality and morbidity occurring due to CARDS. Attention should be also given on molecular drug targets that possibly will help to develop efficient cure for COVID-19-associated ARDS.