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Advanced Neurology Multiple sclerosis: Immunopathogenesis

necrosis factor-alpha (TNFα), reactive oxygen species proteins in brain tissue have been observed in autopsies
(ROS), and reactive nitrogen species (RNS). This type from MS-affected individuals . MS becomes a clinically
[45]
of astrocyte reaction is thought to be an innate immune progressive disease when the extent of lesions exceeds the
response of the brain to various injuries . neuroplasticity of the CNS and symptoms of disability
[5]
begin to appear . These changes may explain why disease-
[46]
Mitochondrial dysfunction is also associated with
neuronal damage in MS. Mitochondria are highly modifying treatments are effective in RRMS but not in PMS,
as treatment starts late, when neurodegeneration is already
susceptible to ROS-induced oxidative damage. The pervasive and CNS functional reserve has diminished. This
inflammatory process disrupts the movement of is also confirmed by recent studies on the administration
mitochondria from the soma to the axon due to kinesin of the highly effective disease-modifying therapy, which
dysfunction, and it has been revealed that stimulating was started in the early stages of PMS when the patients
mitochondrial supply from the soma into axons reduced had reduced disability progression [5,47] . At the time of
neuroaxonal damage [33,34] . Another study called attention writing, there are no specific guidelines or statistically
to changes in motor proteins responsible for the movement significant measurements that could be used to determine
of mitochondria to axons and that neurons in deep cortical progression of MS, although the search for reliable and
[35]
layers have mitochondria with mtDNA deletions . objective measures of the progression of MS is ongoing .
[48]
Analyses of biomarkers in CSF have shown that CSF lactate Early detection of SPMS has been sought through the use
concentration is correlated with the rate of progression of of algorithms and biomarkers . The expanded disability
[11]
MS, reinforcing mitochondrial involvement in PPMS . status scale (EDSS) score remains the primary measure
[36]
Iron is an important component in the process of myelin of clinical MS. Various imaging biomarkers are being
formation by oligodendrocytes; it is first stored in ferritin investigated to better detect and monitor the progression of
and then in the myelin sheath . Iron metabolism is MS in the clinic . At present, new T2 and/or gadolinium
[37]
[49]
susceptible to disruption by inflammation, resulting in contrast of the lesions in conventional MRI is considered
the release of iron from myelin and accumulation in the the most important marker of clinical MS relapse.
immediate environment, which in turn leads to iron-induced Additional imaging biomarkers, such as leptomeningeal
oxidative stress. Iron accumulation is a major feature of MS contrast enhancement, newly highlighted SELs within
and is associated with neuronal degeneration . Therefore, the white matter, and T2 lesion volume, show strong
[38]
remyelination does not confer wide-scale protection correlation with clinical and/or MRI measures of MS
when axon degeneration is already underway, but it progression . SELs have been found to correlate with signs
[11]
supports and protects axons from further deterioration of acute axonal injury in the environment . SELs occur
[50]
by providing supportive factors such as energy sources for more frequently in PMS than in RRMS . It is important
[5]
the production of ATP [39,40] . Demyelination is particularly to note that another MRI study found that the corners of
pronounced in SEL, indicating that chronic inflammation SELs contain active microglia/macrophages, which often
prevents remyelination, which in turn affects axonal have iron deposition. However, a more recent study using
survival . Studies conducted with PET have shown that the TMEM119 marker, which is selective for microglia,
[41]
patients with a higher potential for dynamic remyelination showed that microglial cells predominate in SELs . Global
[32]
tend to have lower levels of clinical disability . The brain atrophy, SELs, and inflammation mainly triggered by
[42]
rate of myelin repair varies in patients depending on the microglia/macrophages are the main pathological features
presence of oligodendrocyte progenitor cells and their of PMS . At the edges of SELs, activated microglia are
[5]
ability to mature into oligodendrocytes . Remyelination- involved in the failure of remyelination, which in turn
[43]
stimulating treatment may prove to be very effective, but leads to additional destruction of adjacent neural tissue .
[51]
the consensus remains that therapies need to be initiated
Offering simple and widespread accessibility as well as
before neurodegeneration begins . In another study, management and accurate diagnostic prospects, fluid-based
[40]
inflammation of neuronal tissue in mice and humans was biomarkers are at the forefront of current research, boasting
found to lead to induction and toxic accumulation of the a huge potential in MS diagnosis. In a review, Kaisey et al.
synaptic protein Bassoon (Bsn). Genetic disruption of Bsn described a plethora of laboratory diagnostic biomarkers .
[52]
and pharmacological proteosome activation has resulted Oligoclonal bands in CSF are an important biomarker
in improved clearance of Bsn deposits and increased based on the McDonald diagnostic criteria but have limited
neuronal survival .
[44]
[12]
utility as a marker of progression in RRMS and SPMS .
Misfolding of cellular prion proteins has been cited Some cytoskeletal proteins, discovery of neurofilament
as one of the factors contributing to neurodegeneration. light chains (NfL), glial fibrillary acid protein, and kappa-
In addition, citrullination and disruption of myelin free light chains (κFLC) were considered potential sensitive
Volume 2 Issue 3 (2023) 4 https://doi.org/10.36922/an.1319