The Possible Role of Neural Cell Apoptosis in Multiple Sclerosis

Abstract

The etiology of multiple sclerosis (MS), a demyelinating disease affecting the central nervous system (CNS), remains obscure. Although apoptosis of oligodendrocytes and neurons has been observed in MS lesions, the contribution of this cell death process to disease pathogenesis remains controversial. It is usually considered that MS-associated demyelination and axonal degeneration result from neuroinflammation and an autoimmune process targeting myelin proteins. However, experimental data indicate that oligodendrocyte and/or neuronal cell death may indeed precede the development of inflammation and autoimmunity. These findings raise the question as to whether neural cell apoptosis is the key event initiating and/or driving the pathological cascade, leading to clinical functional deficits in MS. Similarly, regarding axonal damage, a key pathological feature of MS lesions, the roles of inflammation-independent and cell autonomous neuronal processes need to be further explored. While oligodendrocyte and neuronal loss in MS may not necessarily be mutually exclusive, particular attention should be given to the role of neuronal apoptosis in the development of axonal loss. If proven, MS could be viewed primarily as a neurodegenerative disease accompanied by a secondary neuroinflammatory and autoimmune process.

Comparing Single-Cell Transcriptomes of Blood and Cerebrospinal Fluid Leukocytes in Multiple Sclerosis

“…Table 3 outlines the top 10 upregulated gene ontology terms observed in MS compared to IIH single cells, with a focus on blood and CSF. In both blood and CSF, several biological processes (BP) related to cellular differentiation and apoptotic regulation stand out, including positive regulation of myoblast and endothelial cell differentiation, along with positive regulation of fibroblast apoptotic processes [6]. These findings suggest potential alterations in tissue remodeling and cellular survival mechanisms.…”

“…Furthermore, genes like TSC22D3 and CASK may contribute to various cellular processes, including transcriptional regulation and synaptic function, highlighting the multifaceted nature of the molecular alterations observed in MS compared to IIH. In both blood and CSF, several biological processes (BP) related to cellular differentiation and apoptotic regulation stand out, including positive regulation of myoblast and endothelial cell differentiation, along with positive regulation of fibroblast apoptotic processes [6]. These findings suggest potential alterations in tissue remodeling and cellular survival mechanisms.…”

Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis

“…Neuron-specific activation of necroptosis was reported recently in MS cortical grey matter [ 16 ]. The IgG antibody-induced complement activation and neuronal apoptosis may be a novel mechanism for axonal loss and neuronal degeneration in MS. Neuronal degeneration and white matter demyelination can be independent events in the disease [ 33 ]. Progressive MS CSF has been shown to induce demyelination and neuronal apoptosis [ 34 , 35 ].…”

BMP7 alleviates trigeminal neuralgia by reducing oligodendrocyte apoptosis and demyelination

“…Both microglia [ 47 , 48 ] and astrocytes [ 49 , 50 ] can contribute to demyelination by influencing oligodendrocytes. Moreover, the precise relationship between demyelination and neuron loss remains unresolved [ 51 ]. In this study, we explored that the overexpression of BMP7 improved demyelination and mitigated the allodynia by enhancing oligodendrocyte survival, but whether it exerted influences through on other cells needs further investigation.…”