Cellular Reprogramming and Its Potential Application in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) has become the most common age-related dementia in the world and is currently incurable. Although many efforts have been made, the underlying mechanisms of AD remain unclear. Extracellular amyloid-beta deposition, intracellular tau hyperphosphorylation, neuronal death, glial cell activation, white matter damage, blood–brain barrier disruption, and other mechanisms all take part in this complicated disease, making it difficult to find an effective therapy. In the study of therapeutic methods, how to restore functional neurons and integrate myelin becomes the main point. In recent years, with the improvement and maturity of induced pluripotent stem cell technology and direct cell reprogramming technology, it has become possible to induce non-neuronal cells, such as fibroblasts or glial cells, directly into neuronal cells in vitro and in vivo. Remarkably, the induced neurons are functional and capable of entering the local neural net. These encouraging results provide a potential new approach for AD therapy. In this review, we summarized the characteristics of AD, the reprogramming technique, and the current research on the application of cellular reprogramming in AD. The existing problems regarding cellular reprogramming and its therapeutic potential for AD were also reviewed.

Integrating a quinone substructure into histone deacetylase inhibitors to cope with Alzheimer's disease and cancer

“…A potential strategy for modifying the course of AD involves the utilization of small molecules able to induce the proliferation and/or differentiation of neural progenitor cells (NPCs), a potential source of new neurons, to mitigate cognitive impairments and counteract neurodegeneration. 40,41 In fact, NPCs are multipotent cells that can generate neurons, astrocytes, and oligodendrocytes, and quinone-based compounds, such as vitamin K derivatives, as well as HDACIs, are known to induce the differentiation of NPCs into neuronal cells. 16,42…”

“…A potential strategy for modifying the course of AD involves the utilization of small molecules able to induce the proliferation and/or differentiation of neural progenitor cells (NPCs), a potential source of new neurons, to mitigate cognitive impairments and counteract neurodegeneration. 40,41 In fact, NPCs are multipotent cells that can generate neurons, astrocytes, and oligodendrocytes, and quinone-based compounds, such as vitamin K derivatives, as well as HDACIs, are known to induce the differentiation of NPCs into neuronal cells. 16,42 Therefore, to investigate the effect of compound 8 on NPCs proliferation and differentiation, experiments were performed on an in vitro model of neurospheres (i.e., floating cultures of NSCs and neuronal, astrocytic, and oligodendrocytic progenitors at different stages of maturation) derived from the sub-ventricular zone (SVZ) of 8-months-old C57BL/6N wild-type male mice (Mus musculus).…”

Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer’s disease in APP/PS1 mouse

“…Accumulation of Aβ42/43 further activates microglia and inflammatory response and leads to mitochondrial damage, energy metabolism disorder, oxidative stress injury, and activation of apoptotic pathways. In addition, the inflammatory response can activate protein kinase, promote the abnormal phosphorylation of tau protein, and make it aggregate to form double-stranded helical filaments and neurofibrillary tangles, resulting in axonal degeneration and neuronal death [ 1 , 5 ].…”