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Advanced Neurology SARS-CoV-2 in age-associated neurodegeneration

stress-induced UPR deregulation plays a pivotal role in lipopolysaccharides and the subsequent formation
age-associated neurodegeneration. SARS-CoV-2 proteins, of α-synuclein deposits in the enteric nerve. Viral
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including the spike protein, ORF8, and NSP3.1, significantly persistence in intestinal cells or heightened inflammation
impact UPR pathways, potentially exacerbating the may also decrease the abundance of commensal bacteria,
formation of protein aggregates characteristic of such as Ruminococcaceae and Lachnospiraceae, while
neurodegenerative diseases such as Parkinson’s disease, inducing the colonization of pathobionts, such as
AD, and amyotrophic lateral sclerosis. These findings Enterobacteriaceae and Desulfovibrionaceae. This
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underscore the importance of understanding how viral phenomenon is associated with increased levels of
influences on cellular stress responses may accelerate the peripheral inflammatory cytokines in the gut, including
onset or progression of these debilitating conditions. IL-6, TNF-α, C-reactive protein, IL-1β, and IL-2, which
are correlated with psychiatric and neurodegenerative
6.4. Gut–brain dysbiosis in COVID-19: Implications disorders. Notably, these peripheral cytokines can reach the
for neurodegenerations CNS through the BBB or through the circumventricular
In the intricate harmony of human health, the gut organs, contributing to microglial activation. 123,124
microbiome plays a crucial role in maintaining brain Along with the gut-brain axis, the gut-lung axis also plays
function. Over the past few decades, it has become evident a critical role in neurological manifestations. Multi-omics
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that viral infections, particularly SARS-CoV-2, have a data collected from COVID-19 patients suggest that acute
profound impact on the mammalian gut. Impairment SARS-CoV-2 infection not only impacts species abundance
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of the gut microbiota can trigger numerous neurological and diversity but also impairs secondary metabolite
signals that may lead to long-term neurological sequelae in production, which may directly affect neurotransmitter
COVID-19 patients. These mechanisms are regulated by release and synapse formation. Therefore, treatments with
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inflammatory cytokines, GI hormones, neurotransmitters prebiotics, probiotics, and fecal microbial transplantation
(e.g., 5-hydroxytryptamine), and short-chain fatty acids
secreted by intestinal epithelial cells. 115 could open up new therapeutic avenues. However, further
evidence showing a direct correlation between long COVID
The microbiota–gut–brain axis is a bidirectional and gut dysbiosis is essential.
communication pathway that influences inflammatory
signaling. Gut-brain dysbiosis is often associated with 7. Advancement in therapeutic approaches
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the manifestation of neurological disorders, including AD, for neurological disorders associated with
Parkinson’s disease, and amyotrophic lateral sclerosis. long-term COVID
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During the course of the COVID-19 infection, viral
replication can occur within the GI tract for an extended The emergence of SARS-CoV-2, which triggered COVID-
period. Once the infection resolves, microbiota dysbiosis 19-associated neurological deficits, stands as one of the
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may develop. This imbalance in gut bacterial populations greatest medical emergencies of recent times. Substantial
can lead to long-term symptoms. SARS-CoV-2 enters the investment in life sciences over the past few decades
intestine through ACE2 receptors located on the brush has facilitated a prompt scientific response, including
border of enterocytes in the small intestine, making advancements in viral characterization, testing, and
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these cells susceptible to infection. ACE2 also forms a sequencing. This rapid progress permitted the development
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complex with the amino acid transporter B0AT1, which of highly effective vaccines within a short period, offering
mediates the uptake of tryptophan into intestinal cells. partial protection. However, contrary to popular belief,
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Conversely, mTOR, an essential sensor of intracellular available drug treatments have delivered limited benefits
amino acids, regulates gut microbial composition. Thus, the so far. Due to the enormity of the pandemic, clinical
downregulation of the ACE2 receptor due to COVID-19 trials primarily focused on acute symptoms, leaving some
infection reduces the secretion of antimicrobial peptides, potential therapies insufficiently tested. At present, published
further enhancing peripheral immune deregulation. 120 therapies provide evidence supporting the treatment of early
symptoms, but the understanding of COVID-19’s impact on
Although substantial evidence is still lacking regarding
increased susceptibility to chronic neurological diseases, complex organs like the brain remains limited. Therapeutics
for long-term COVID-associated neurological symptoms
such as Parkinson’s disease, following COVID-19 are under investigation, including anti-viral therapies,
infection, it is speculated that SARS-CoV-2 infection could anti-inflammatory therapies, neutralizing antibodies, and
predispose patients to long-term neurological disorders. 125
Such an effect could occur through ACE2 dysfunction, anti-coagulant therapies.
which may compromise the integrity of the intestinal Significant efforts are underway to identify biomarkers
barrier. This event may lead to elevated levels of circulating associated with biological aging, which could serve as

Volume 3 Issue 4 (2024) 15 doi: 10.36922/an.4267