Page 68 - AN-2-2

Advanced Neurology Role of immunosuppressants in autism

in the copy number of the UBE3A gene. This, in turn, maintenance of synapses [75,76] . However, excessive mTOR
causes an increase in the amount of Ube3A and E6AP signaling can also lead to the formation of too many
that is present in dendritic arborization while the brain is synapses, which can result in neural dysfunction and
developing. There is evidence that caspases have a role in cognitive impairments. To prevent this, mTOR signaling
the initiation and differentiation of monocytes, as well as is also involved in the process of synaptic pruning, by
the activation and proliferation of T lymphocytes and promoting the elimination of weaker or unnecessary
[71]
other hematopoietic cells. Caspase-1 is necessary for the synapses . Dysregulation of synaptic pruning and mTOR
[77]
development of the inflammasome protein scaffold as well signaling has been implicated in various neurological
as the subsequent cleavage and activation of the potent disorders, such as ASD, schizophrenia, and epilepsy. For
pro-inflammatory cytokine’s IL-1b and IL-18 . Caspase-1 example, excessive synaptic pruning during early brain
[72]
is responsible for initiating innate immune responses, and development has been linked to the pathogenesis of
the subsequent production of IL-1b and IL-18 is what schizophrenia, while impaired synaptic pruning has been
triggers adaptive immune responses mediated by Th1 and associated with ASD . The balance between synaptic
[78]
Th17. Both caspase-2 and caspase-12, when activated, can growth and pruning is critical for normal brain function
play a role in either sensing or causing cellular damage . and plasticity. Several studies have shown that disruptions
[73]
The study suggests that the activation of two proteases may in this balance can lead to cognitive impairments and
show cellular stress events in people with ASD, which can behavioral abnormalities. For example, excessive pruning
help identify related issues. of synapses in the prefrontal cortex during adolescence has
With the use of the reverse transcription polymerase been linked to the onset of psychiatric disorders, such as
chain reaction (RT-PCR) method, the author claims depression and anxiety. mTOR signaling is regulated by a
that there is an increase in the pro-inflammatory variety of cellular and environmental cues, such as growth
[78]
caspases-1, -4, -5, and cellular stress-related caspase-2 factors, nutrients, and stress . Dysregulation of these
genes in the peripheral blood mononuclear cells of ASD signals can lead to abnormal mTOR activity and synaptic
patients. In conclusion, the involvement of caspases is dysfunction. For example, chronic stress has been shown to
negatively involved in nigrostriatal dopaminergic pathway, dysregulate mTOR signaling and impair synaptic plasticity
leading to autism. In addition, the author claims that in the hippocampus, a brain region critical for learning and
[79]
caspase-7 and caspase-12 protein levels were also shown memory . Therapeutic interventions that target mTOR
to be higher in ASD patients and the loss of caspase-3 in signaling have shown promise in treating neurological
[74]
the midbrain which is involved in deletion of unnecessary disorders. For example, rapamycin, which inhibits mTOR
connection of new neurons with pre-existing neurons signaling, has been shown to improve synaptic plasticity
(pruning) during the neurodevelopmental phase of baby and cognitive function in animal models of Alzheimer’s
[80]
in mother can cause neurodevelopmental disorder and has disease and traumatic brain injury . However, the use
been linked to ASD. This indicates a role for caspase in the of such drugs in humans requires further investigation,
development of autism, and further work on these caspases as mTOR signaling has diverse functions and targeting it
would shed light on attenuating symptoms through the may have unintended consequences. In summary, synaptic
treatment of autism. pruning and mTOR signaling are closely related, with
mTOR signaling playing a crucial role in both the formation
3.1.1. Synaptic pruning is related to mTOR signaling and elimination of synapses during brain development and

Synaptic pruning is a process by which the brain eliminates plasticity.
unnecessary or weak synaptic connections between 3.2. Natural killer cells
neurons. This process is essential for the development and
refinement of neural circuits during early brain development Large granular lymphocytes, also known as NK cells,
and is also implicated in learning and memory. mTOR play a role in immunological control and act as a line
signaling is a molecular pathway that plays a crucial role of defense against virus-infected cells and malignant
in regulating cellular growth and metabolism, including tumors. In addition, autoimmune disorders such as
neuronal development and plasticity . It has been shown lupus erythematosus , multiple sclerosis , rheumatoid
[24]
[44]
[25]
that mTOR signaling is involved in the process of synaptic arthritis , and Sjogren’s syndrome have all been linked
[26]
[26]
pruning. During brain development, mTOR signaling is to decreased activity . NK cells are thought to be involved
[28]
activated in response to synaptic activity and regulates in autism due to the fact that viral infections and altered
the growth and maturation of dendrites and synapses. immune responses have also been linked to it. NK cells are
This activation of mTOR signaling triggers the synthesis also thought to be associated with autoimmune disorders
of new proteins that are required for the formation and due to their role in the body’s fundamental defense system
Volume 2 Issue 2 (2023) 8 https://doi.org/10.36922/an.391