Implications of white matter damage in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal-glial interactions. Previous studies have suggested that WM damage may occur prior to the death of motor neurons, and thus may be considered an early indicator for the diagnosis and prognosis of ALS. However, the exact molecular mechanisms underlying early-onset WM damage in ALS have yet to be elucidated. The present review explored the detailed anatomy of WM and identified several pathological mechanisms that may be implicated in WM damage in ALS. In addition, it associated the pathophysiological alterations of WM, which may contribute to motor neuron death in ALS, with similar mechanisms of WM damage that are involved in multiple sclerosis (MS). Furthermore, the early detection of WM damage in ALS, using neuroimaging techniques, may lead to earlier therapeutic intervention, using immunomodulatory treatment strategies similar to those used in relapsing-remitting MS, aimed at delaying WM damage in ALS. Early therapeutic approaches may have the potential to delay motor neuron damage and thus prolong the survival of patients with ALS. The therapeutic interventions that are currently available for ALS are only marginally effective. However, early intervention with immunomodulatory drugs may slow the progression of WM damage in the early stages of ALS, thus delaying motor neuron death and increasing the life expectancy of patients with ALS.

Differences in splicing defects between the grey and white matter in myotonic dystrophy type 1 patients

“…First, we used ALS brain samples as the disease control. ALS tissues show splicing deregulation [34] and ALS brains may also display significant changes in WM and GM [35]. Our previous study showed statistical significance in the splicing defects in the temporal lobe of DM1 compared with either disease controls (7 out of 9 samples were from ALS) or healthy controls [4].…”

Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?

“…Similarly, endogenous Nrf2 activation is clearly evident in oligodendrocytes in multiple sclerosis [ 222 ], yet Nrf2 signalling in oligodendrocytes has not been assessed in any other disease. This may be pertinent for amyotrophic lateral sclerosis, which also involves demyelination [ 271 ]. Further evidence is required to determine in which cells Nrf2 activation occurs in response to treatments targeting Nrf2.…”

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

“…FA measures the movement of water molecules within tissues and was interpreted to reflect the integrity of WM microstructure in brain (Agosta et al, 2010;Basser & Pierpaoli, 2011). In previous neuroimaging studies, alterations in FA have been considered to be associated with various WM pathologic features, such as ischemia, myelination, axonal damage, inflammation, edema (Pfefferbaum et al, 2000;Toosy et al, 2003;T. Zhou et al, 2017), and so forth.…”