JAK/STAT (Janus-kinase/signal activator and transducer of
transcription pathways)
These are a collection of intracellular processes that regulate gene
expression. It’s one of the most essential signaling channels for
transmitting cytokine-induced signals from the cell surface.
Inflammation of the central nervous system is also influenced by this
route. STAT is phosphorylated by JAK when it is activated, and then it
translocates into the nuclease to modify the expression of a specific
gene. Depending on the STAT isoform, various anti-inflammatory,
pro-inflammatory, proliferative, or apoptotic proteins can be expressed.
The JAK-STAT pathway’s dysregulation in inflammation and
neurodegenerative illnesses makes it a key player in the majority of
brain diseases. STAT1 activity has been linked to a decrease in cell
viability in the brain, whereas STAT3 is thought to be a pro-survival
factor (Planas, Gorina & Chamorro, 2006). Many investigations have
shown that after SAH, STAT1 and STAT2, as well as their activators JAK1
and JAK2, are active (Osuka et al., 2006; Samraj, Müller, Grell &
Edvinsson, 2014). (Gorina, Petegnief, Chamorro & Planas, 2005)
discovered that anti-inflammatory cytokines such as IL-10 activated
STAT3 but not STAT1, whereas pro-inflammatory signals such as IFN-γ
(interferon) activated both STAT1 and not STAT3, and IL-6 activated both
STAT1 and STAT3. Tyrphostin, a JAK2 inhibitor, was discovered to be
involved in the reported activation of STATs following IL-6 and IFN-γ,
but not following IL-10 (AG490). Oxidative stress, which is produced in
the ischemic brain and contributes to ischemic brain damage, can also
activate STATs. The Gorina, Petegnief, Chamorro, and Planas
investigation went on to show that JAK2/STAT1 activation causes cell
death, which is consistent with the notion that STAT1 is activated in
neurons after ischemia and plays a role in ischemic brain injury
(Takagi, Harada, Chiarugi & Moskowitz, 2002). According to Osuka et
al., after SAH, IL-6 expression causes JAK1-STAT3 phosphorylation, which
leads to the overexpression of COX-2, which is responsible for the
synthesis of PGI, an enzyme recognized for reducing vasospasm by
promoting vasodilation and inhibiting platelet aggregation. STAT1 and
STAT3 are activated by oxidative stress and certain cytokines through a
JAK2-dependent pathway (Planas, Gorina & Chamorro, 2006). A number of
pro-inflammatory cytokines, including IL-10, activate STAT3, although
others, such as interferon, induce STAT1 phosphorylation through the
JAK2 pathway (Regis, Pensa, Boselli, Novelli & Poli, 2008). Melatonin
therapy activates JAK1 and enhances the phosphorylation of STAT3,
according to(Li, Yang, Sun & Hang, 2019). This effect is abolished by a
JAK1 antagonist, demonstrating that JAK activation is implicated in
Melatonin’s protective benefits against EBI after SAH. Nonetheless, when
discussing events following SAH, the role of the JAK/STAT system remains
a subject of many unknowns, necessitating more research in this field.