Hypothesized neuroprotective effect of minocycline against COVID-19-induced stroke and neurological dysfunction: possible role of matrix metalloprotease signaling pathway.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.

Cannabinoids Δ9-tetrahydrocannabinol and cannabidiol may be effective against methamphetamine induced mitochondrial dysfunction and inflammation by modulation of Toll-like type-4(Toll-like 4) receptors and NF-κB signaling.

The neurodegeneration, neuro-inflammation and mitochondrial dysfunction which occur by methamphetamine (METH) abuse or administration are serious and motivation therapeutic approaches for inhibition of these types of neurodegeneration. As we know, METH through Toll-like receptors (TLRs), specially type 4, and NF-κB signaling pathway causes neuro-inflammation and mitochondrial dysfunction. Neuroprotective approach for management of METH-induced neurodegeneration, inflammation and mitochondrial dysfunction, through a novel neuroprotective agent is continuously being superior to any kind of other therapeutic strategy. Therefore, the clarification, introduction and development of efficacious novel neuroprotective agent are demanded. During recent years, using new neuroprotective agent with therapeutic probability for treatment of METH-induced neuro-inflammation and mitochondrial dysfunction has been astoundingly increased. Previous studies have stated the neuroprotective and anti-inflammatory roles ofcannabinoid derivate such as cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ9-THC) in multiple neurodegenerative events and diseases. According to literature cannabinoid derivate, by inhibition of TLR4 and activation of NF-κB signaling pathway, exerts their anti-inflammatory and neuroprotective effects and cause mitochondrial biogenesis. Thus we hypothesized that by using cannabinoids in METH dependent subject it would provide neuroprotection against METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction and probably can manage sequels of METH-induced neurochemical abuses via modulation of TLR4/NF-κB signaling pathway. In this article, we tried to discuss our hypothesis regarding the possible role of CBD and Δ9-THC, as a potent neuroprotective and anti-inflammatory agents, in inhibition or treatment of METH-induced neurodegeneration, neuro-inflammation and mitochondrial dysfunction through its effects on TLR4/NF-κB signaling pathway.