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INNOSC Theranostics and
Pharmacological Sciences BDNF-AS biomarker in multiple sclerosis

1. Introduction in the CNS. 16,17 Numerous lncRNAs expressed in the CNS
have been found to play critical roles in the functions of
Neurodegeneration refers to the progressive loss of neuronal neural cells, neurodevelopment, and the regeneration
function within the central nervous system (CNS), affecting and differentiation of neural stem cells. Brain-derived
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millions of people and posing a major medical challenge neurotrophic factor-antisense (BDNF-AS), a type of
worldwide. Multiple sclerosis (MS) is a neurodegenerative lncRNA, is known for its role in regulating the expression
1
condition that results in the degeneration of neuronal and function of the neurotrophin protein brain-derived
2
axons and gliosis within the CNS. According to the 2013 neurotrophic factor (BDNF) within the CNS. 19,20
MS Atlas, the Middle Eastern, and North African nations
3
are classified as low- to moderate-risk regions for MS. It The downregulation of BDNF-AS has been shown
is characterized by ongoing inflammation within the CNS, to inversely upregulate BDNF protein levels, resulting
which results in tissue damage, leading to brain and spinal in a pro-neuronal effect by stimulating neuronal cell
cord atrophy and irreversible neurological impairment. growth and differentiation. 21,22 This effect is believed to
4
MS is considered the most prevalent neurological disease be mediated by BDNF, which is recognized as a critical
among young adults, affecting more than 2.5 million people regulator of neuronal plasticity, making it one of the most
23
globally. In Africa and the Middle East, Egypt has the significant proteins in this context. Importantly, BDNF is
5
24
highest incidence of MS, with 59,671 documented patients. 6 overexpressed by immune cells in MS lesions, and other
studies have demonstrated that BDNF protein levels are
The majority (~85 – 90%) of MS cases initially present
a relapsing-remitting disease course (i.e., RRMS), whereas reduced simultaneously in the serum or plasma of MS
Therefore, the level of
patients compared to controls.
25-30
10% of cases develop primary progressive MS (PPMS). BDNF-AS has become an important focus of research in
About 90% of RRMS patients eventually progress to MS in investigating its role in regulating BDNF in MS and
secondary progressive disease (i.e., SPMS). The causes
7
of progressive MS are not as well understood as those of its potential pathophysiological function.
relapsing forms, which involve disruptions in the immune To our knowledge, the expression of BDNF-AS has
system. While inflammation is the primary driver of MS not been thoroughly investigated in neurological diseases
8
activity, neurodegeneration is also thought to play a major within patient blood samples; it has only been analyzed in
role in the disease progression. 9 cell models and postmortem patient tissues. Moreover, the
Long non-coding RNAs (lncRNAs) are transcripts only study on BDNF-AS in MS focused on whole blood
longer than 200 nucleotides that do not have the functional from RRMS patients, where no significant differences were
31
ability to code for proteins. 10,11 The functions of lncRNAs, found compared to controls. Therefore, our study aims to
such as those of protein-coding genes, are diverse and can be the first to comprehensively investigate the expression
vary greatly. LncRNAs have been shown to play a role in of BDNF-AS across different MS subtypes and explore
12
various significant biological processes through interactions its relationship with disease prognostic parameters. This
with DNA or chromatin, modulation of regulatory or research will contribute to understanding the role of
signaling pathways, and the regulation of other types of BDNF in MS and examine the diagnostic and prognostic
ribonucleic acid (RNAs). Some lncRNAs may function as potential of BDNF-AS in MS.
13
decoys, binding to effector proteins and preventing them 2. Methods
from carrying out their intended functions by diverting
them from their target sites. Certain lncRNAs contain 2.1. Subject recruitment
10
so-called “microRNA (miRNA) response elements,” which This study involved 54 individuals diagnosed with MS
are complementary binding sites for miRNAs. These at multiple stages of the disease alongside 20 healthy
lncRNAs are known as competitive endogenous RNAs volunteers, carefully matched for gender and age.
(ceRNAs), which act as molecular sponges for miRNAs, Recruitment occurred between January and May 2021, with
inhibiting their ability to reach target genes. Despite participants sourced from the MS Research Unit at Cairo
14
typically having lower expression levels than messenger University Hospital in Kasr Al-Ainy, Cairo, Egypt. Written
RNAs, lncRNAs often display more distinctive expression informed consent was obtained from all participants, both
patterns specific to certain tissues and cells, suggesting that patients and controls, before their involvement. Ethical
they play crucial roles in cell-specific pathways. 15 approval (approval number: 19922) was granted by the

The CNS is composed of a variety of cell types with Board of Ethical Committee, Suez University, Egypt,
distinct morphologies and functions. Neurotrophic ensuring compliance with the ethical principles outlined
lncRNAs are believed to influence the genetic and in the Declarations of Helsinki (1964) and its subsequent
epigenetic regulation of the expression of genes involved revisions. 32

Volume 8 Issue 1 (2025) 92 doi: 10.36922/itps.4407