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Bioinformatics of the Brain

extracellular vesicles safely exhibit promising results on AD treatment and

the life quality of the subjected patients [97, 99, 101, 102].

2.3.1.5

Preclinical Studies of NSCs in AD Models

Neural stem cells (NSCs) are the second most prevalent stem cell type utilized

in AD-related research, following MSCs. NSC transplantation is able to reg-

ulate various functions, such as attenuation of Aβ and tau pathophysiology,

pacification of neuroinflammation, induction of neurogenesis, reinforcement of

the cerebrovascular system, remediation of synaptic signaling, and secretion of

neurotrophic factors [103]. Studies about NSCs are currently conducted on ro-

dent models in preclinical studies. Outcomes from AD models are spectacular

and predisponent for clinical trials in the near future [103–105].

2.3.2

Parkinson’s Disease (PD)

Parkinson’s disease (PD) is the second most widespread progressive neu-

rodegenerative disorder that results in the deterioration of the dopaminer-

gic (DOPA) neurons in the basal ganglia, or substantia nigra, a section of

the human brain controlling movement. There are a variety of motor and

non-motor dysfunctions, such as tremors, muscle stiffness, slowed movements

(bradykinesia), postural deformities, cognitive deterioration, olfactory dys-

function, neuropsychiatric problems, and systemic pain [103, 106]. A charac-

teristic molecular pathology in PD is the appearance of Lewy bodies, which

are composed of aberrant α-synuclein protein. Unfolded α-synuclein deposits

as stacks inside the presynaptic terminals of DOPA neurons, blocking signal

transmission. Alpha-synuclein aggregation alters the phosphorylation status

of tyrosine hydroxylase (TH), a main enzyme functioning in DOPA biosyn-

thesis [107]. Furthermore, genome-wide studies elicited PD-causative genetic

variations in certain genes like alpha-synuclein gene (SNCA), Parkin RBR

E3 ubiquitin-protein ligase (PRKN), Parkinson protein 7 (PARK7), PTEN-

induced kinase 1 (PINK1), leucine rich-repeat kinase 2 (LRRK2), prosaposin

(PSAP), and glucocerebrosidase (GBA1) [103, 108].

Administration of the DOPA precursor (Levodopa) is the only applica-

ble treatment to decelerate the disease progression and moderate the motor

symptoms. However, there is still a need for effective treatment strategies that

provide more permanent solutions rather than just evading symptoms. Even-

tually, stem cells emerge as new therapeutic tools and as satisfying PD models

to understand molecular pathways in depth.

2.3.2.1

Organoids and PSCs for Modeling PD

Embryonic stem cells and patient-derived iPSCs provide a feasible platform

to investigate the molecular mechanisms underlying Parkinson’s disease oc-

currence, progression, and interruption. Additionally, pluripotent stem cells

(PSCs) often facilitate cell-based drug screening [109].