Alzheimer’s disease: Pathophysiology and dental pulp stem cells therapeutic prospects

Abstract

Alzheimer’s disease (AD) is a destructive neurodegenerative disease with the progressive dysfunction, structural disorders and decreased numbers of neurons in the brain, which leads to long-term memory impairment and cognitive decline. There is a growing consensus that the development of AD has several molecular mechanisms similar to those of other neurodegenerative diseases, including excessive accumulation of misfolded proteins and neurotoxic substances produced by hyperactivated microglia. Nonetheless, there is currently a lack of effective drug candidates to delay or prevent the progression of the disease. Based on the excellent regenerative and reparative capabilities of stem cells, the application of them to repair or replace injured neurons carries enormous promise. Dental pulp stem cells (DPSCs), originated from ectomesenchyme of the cranial neural crest, hold a remarkable potential for neuronal differentiation, and additionally express a variety of neurotrophic factors that contribute to a protective effect on injured neuronal cells. Notably, DPSCs can also express immunoregulatory factors to control neuroinflammation and potentiate the regeneration and recovery of injured neurons. These extraordinary features along with accessibility make DPSCs an attractive source of postnatal stem cells for the regeneration of neurons or protection of existing neural circuitry in the neurodegenerative diseases. The present reviews the latest research advance in the pathophysiology of AD and elaborate the neurodifferentiation and neuroprotective properties of DPSCs as well as their application prospects in AD.

Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer’s disease

“…Since the most prominent molecular pathology of AD is the neurotoxicity of aggregate Aβ and hyperphosphorylated tau protein, which jointly damage neurons and ultimately lead to cognitive decline, we performed immunofluorescence staining to assess whether hDPSCs had modified their progression. 1 The results revealed that the pathological Aβ aggregation and the expression of phosphorylated Tau protein (AT8) in the hippocampus of hDPSCs-treated AD mice were much lesser than those in AD-PBS mice (Fig. 6c, d ).…”

“…Prolonged periods of uncontrolled intracerebral homeostatic imbalances lead to abnormal activation of microglia and chronic neuroinflammation, which can further exacerbate neurodegeneration and cognitive impairment. 1 , 14 To investigate the effects of hDPSCs on microglia abnormal activation pathology, we induced BV2 cells with bacterial lipopolysaccharide (LPS) stimulation, which is considered the gold standard for microglia activation. 15 BV2 cells were challenged with different conditions of LPS to determine the best induced effects.…”

“…As the most common cause of dementia, Alzheimer’s disease (AD) is a highly disabling disorder characterized by progressive neurodegeneration and irreversible cognitive impairment, making up approximately 60% to 80% of global dementia cases. 1 However, despite high prevalence and extensive research efforts, there are currently no curative treatments that can prevent and/or delay disease progression, underscoring the urgent need for novel therapeutic strategies.…”

Nerve growth factor promote osteogenic differentiation of dental pulp stem cells through MEK/ERK signalling pathways

“…DPSCs have demonstrated clinical potential not only in dentistry but also in the treatment of various diseases, including craniofacial bone defects, muscle regeneration, myocardial infarction, Alzheimer's disease, nervous system injuries, Parkinson's disease, stress urinary incontinence, osteoarthritis and liver diseases. [16][17][18][19][20][21][22][23][24] This study aimed to investigate whether co-administration of DPSCs and human umbilical vein endothelial cells (HUVECs) could enhance the therapeutic effects of stem cells for critical hindlimb ischemia, compared to the effects of either DPSCs or HUVECs alone. The combination therapy of DPSCs and HUVECs resulted in significantly higher blood flow and reduced ischemic damage compared to the individual administration of DPSCs or HUVECs.…”

“…Due to DPSCs' multidirectional differentiation potential and easy accessibility, their application in bone tissue engineering is currently under extensive exploration. DPSCs have demonstrated clinical potential not only in dentistry but also in the treatment of various diseases, including craniofacial bone defects, muscle regeneration, myocardial infarction, Alzheimer's disease, nervous system injuries, Parkinson's disease, stress urinary incontinence, osteoarthritis and liver diseases 16–24 …”