Therapeutic Potential of Stem Cells in Neurodegenerative Diseases

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TABLE 2.1

How various stem cell types are utilized in neurodegenerative disease

research

Activity

Purpose

Stem cell type

Clinical research Cell therapy and transplantation

ESCs, iPSCs

Neuroprotective effects

MSCs

Modulation of

neuroinflammation and immune

responses

MSCs, HSCs

Basic and

translational

research

Neurodegenerative disease

modeling

ESCs, iPSCs

Drug screening

ESCs, iPSCs

Understanding neurogenesis and

neuronal pathways

NSCs, ESCs, iPSCs

Activation of neurogenesis and

promotion neuroregeneration

NSCs, iPSCs

of new strategies and potential

therapeutic targets in vitro/vivo

Various

Neurotrophic effects

MSCs

Brain organoids/spheroids

iPSCs, ESCs

The application of certain stem cell types in research activities related

to widespread neurodegenerative diseases is discussed in more detail in the

following titles.

2.3.1

Alzheimer’s Disease (AD)

Alzheimer’s disease (AD) is the leading dementia-causing brain pathology,

with a rapid increase of approximately 148% in the aging population [34, 35].

AD is characterized by extracellular plaque formation and the accumulation of

intracellular neurofibrillary tangles that impede brain functions, particularly

memory, cognition, and learning. According to the well-accepted pathogenic

mechanism, amyloid β-peptide (Aβ) is formed as a result of faulty proteolytic

cleavage of amyloid precursor protein (APP), a transmembrane protein on

nerve cells. Polymerized amphipathic Aβ molecules occupy synaptic space

as insoluble amyloid plaques, which disrupt synaptic signaling [36, 37]. In

parallel, Aβ accumulation causes hyperphosphorylation of tau protein, which

normally stabilizes microtubules for a proper axonal process. This abnormal

hyperphosphorylation state disrupts conformation and leads to misfolding in

tau protein [38, 39]. Aberrant tau proteins aggregate as insoluble neurofibril-

lary tangles (NFTs) inside the neurons [39, 40]. Eventually, Aβ and tau de-

position together results in neuroinflammation and neurotoxicity within the

brain. While dominant inheritance of the mutations in three major genes (amy-

loid precursor protein (APP) gene, presenilin1 (PSEN1) gene, and presenilin