Alzheimer’s disease is a progressive brain disorder that gradually destroys memory, thinking skills, and the ability to carry out simple tasks. Alzheimer’s is characterized by the buildup of proteins in the brain, forming plaques and tangles that damage nerve cells. The major constituents of amyloid plaques are the β-amyloid peptides consisting of 40 and 42 amino acids, which are derived from the amyloid precursor protein. Neurofibrillary tangles are made up of paired helical filaments consisting of hyperphosphorylated tau protein (phospho-tau). Tau protein, present in the brain in 6 different isoforms, is an intracellular protein that is released upon neuronal death.
Therapeutic drugs for Alzheimer’s Disease (AD) face significant limitations, particularly in advanced stages. Key limitations include:
Currently approved drugs primarily target symptoms and aim to help existing healthy neurons function optimally, but they cannot replace neurons that have already been lost.
As AD progresses and the severity increases, the overall health and functionality of body cells, including those forming the blood-brain barrier (BBB), can decline.
The BBB, which normally regulates the passage of molecules into the brain, can become compromised in AD, making effective drug delivery challenging. This can result in:
Multi-Target Drug Design in Alzheimer’s Disease Treatment: Emerging Technologies, Advantages, Challenges, and Limitations
Neurotrophic Factors: MSCs secrete growth factors like BDNF and GDNF, which are crucial for neuronal survival and function. Mesenchymal Stromal cell therapies for neurodegenerative diseases. https://cmbl.biomedcentral.com/articles/10.1186/s11658-022-00359-z
Anti-inflammatory Effects: MSCs can modulate neuroinflammation by influencing microglia and astrocyte activity, which are key players in AD pathology. Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects.
https://cmbl.biomedcentral.com/articles/10.1186/s11658-022-00359-z
Neuroprotection: MSCs can protect neurons from damage and death, potentially slowing down the progression of neurodegeneration. Mesenchymal stem cell therapy for Alzheimer’s disease.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8426054/
Mitochondrial Function: MSCs may improve mitochondrial function, which is often impaired in AD. Mesenchymal stromal cell therapies for neurodegenerative diseases.
https://pubmed.ncbi.nlm.nih.gov/31054608/
Synapse Stabilization: MSCs can help stabilize synapses, which are crucial for communication between neurons. Mesenchymal stem cells for neurological disorders and mesenchymal stromal cell therapies for neurodegenerative diseases.
https://pubmed.ncbi.nlm.nih.gov/31054608/
MSCs offer a promising avenue for AD treatment due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, and neuroprotective properties. Research suggests MSCs can reduce amyloid-beta (Aβ) deposits, improve neuronal survival, and enhance neurogenesis, potentially slowing disease progression.
Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells’ capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.
Up until now, numerous approaches to therapeutic drugs are encountering unsatisfying outcomes in improving the cognitive performance of Alzheimer’s disease. The reason why drugs are not curing it well is very complex. One of the reasons is unclear pathology. In other words, the pathogenesis of AD is still under investigation. Another reason is that AD is a chronic disease that requires long-term care. This is unlike treatment for acute diseases where short-term drug therapy is viable, and the outcome is timely. As time progresses, the method of drug intake for AD patients needs careful modification. Most importantly, therapeutic drugs are not able to stimulate the regeneration of neural cells that are already damaged. As the level of severity of AD increases, the lack of vitality of body cells also inhibits the effective transportation of drug molecules. Thus, the efficiency and accuracy of drug therapy are highly restrained.
However, stem cell therapy, which has been developed relatively recently, gives hope for better treatment of AD. Stem cell therapy enhances the level of functional recovery in the central nervous system of the brain. By implementing exogenous stem cells, the depleted neuronal circuitry could be repopulated and regenerated. Stem cell therapy is able to reduce neuroinflammation, which is especially important for patients who develop AD after aneurysmal subarachnoid hemorrhage (SAH) because neuroinflammation plays a vital role in injury expansion and brain damage that eventually cause cognitive decline. Stem cell therapy can also eliminate neurofibrillary tangles and abnormal degradation of proteins, and promote mitochondrial transport to improve cognition. In particular, in the early stages of AD, neural stem cells are able to participate extensively in brain homeostasis, which repairs and exhibits pleiotropic intrinsic properties to mitigate and eventually cure AD.
In terms of mechanism of actions, recent research focused on the interplay between amyloid-beta Aβ (and tau), neurons, and glia. Stem cells can induce direct regeneration of neurons and synapses. They can also prevent activation of pro-inflammatory microglia, promote activation of anti-inflammatory microglia, inhibit astrogliosis, and promote nonreactive astrocytes. These effects in return may increase amyloid-beta (Aβ) degradation, decrease the risk of the Aβ cascade, repair injured neurons, and enhance synaptogenesis. Two completed and nine ongoing clinical trials using diverse stem cells and administration methods (intravenous, subcutaneous, and intra-cranial) were found for the treatment of Alzheimer’s disease. Although stem cell therapy shows great potential to become a prospective treatment for Alzheimer’s disease in the future, these studies are still in their early stages and more studies showing safety and efficacy are needed.
View the study: https://journals.lww.com/co-psychiatry/Abstract/2019/03000/Stem_cell_therapies_for_Alzheimer_s_disease__is_it.11.aspx
Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating the regeneration of already-damaged neural cells, and merely provide symptomatic relief. Therefore, a deeper understanding of the mechanism of action of stem cell may contribute to the development of novel and effective therapies. The revolutionary discovery of stem cells has cast a new hope for the development of disease-modifying treatments for AD, in terms of their potency in the replenishment of lost cells via differentiating towards specific lineages, stimulating in situ neurogenesis, and delivering the therapeutic agents to the brain. Herein, firstly, we explore the pathophysiology of AD. Next, we summarize the most recent preclinical stem cell reports designed for AD treatment, their benefits and outcomes according to cell type.
View the study: https://pubmed.ncbi.nlm.nih.gov/30565076/
Unfortunately, numerous clinical trials exploring new therapeutic drugs have encountered disappointing outcomes in terms of improved cognitive performance since they are not capable of halting or stimulating the regeneration of already-damaged neural cells, and merely provide symptomatic relief. Therefore, a deeper understanding of the mechanism of action of stem cell may contribute to the development of novel and effective therapies. The revolutionary discovery of stem cells has cast a new hope for the development of disease-modifying treatments for AD, in terms of their potency in the replenishment of lost cells via differentiating towards specific lineages, stimulating in situ neurogenesis, and delivering the therapeutic agents to the brain. Herein, firstly, we explore the pathophysiology of AD. Next, we summarize the most recent preclinical stem cell reports designed for AD treatment, their benefits and outcomes according to cell type.
View the study: https://pubmed.ncbi.nlm.nih.gov/30565076/
Aging is the greatest risk factor for the onset of AD. For the most part, pharmacological interventions are aimed at relieving the symptoms of AD, but stem cell therapy not only has the potential to generate new neurons and replace damaged neurons but also to modulate the immune system. With further clarification of the mechanisms by which AD progresses, stem cell therapies may well prove to be both safe and effective treatments. In time, more advanced stem cell therapies hold the potential for the clinical treatment of this debilitating disease.
View the study: https://pmc.ncbi.nlm.nih.gov/articles/PMC4227270/
Alzheimer’s disease (AD) is one of the most common causes of dementia and is characterized by gradual loss in memory, language, and cognitive function. The hallmarks of AD include extracellular amyloid deposition, intracellular neuronal fiber entanglement, and neuronal loss. Despite strenuous efforts toward improvement of AD, there remains a lack of effective treatment and current pharmaceutical therapies only alleviate the symptoms for a short period of time. Interestingly, some progress has been achieved in treatment of AD based on mesenchymal stem cell (MSC) transplantation in recent years. MSC transplantation, as a rising therapy, is used as an intervention in AD, because of the enormous potential of MSCs, including differentiation potency, immunoregulatory function, and no immunological rejection. Although numerous strategies have focused on the use of MSCs to replace apoptotic or degenerating neurons, recent studies have implied that MSC-immunoregulation, which modulates the activity state of microglia or astrocytes and mediates neuroinflammation via several transcription factors (NFs) signaling pathways, may act as a major mechanism for the therapeutic efficacy of MSC and be responsible for some of the satisfactory results. In this review, we will focus on the role of MSC-immunoregulation in MSC-based therapy for AD.
View the study: https://www.mdpi.com/1422-0067/22/4/2153
Over the past decade, there has been considerable excitement about using MSCs to treat neurodegenerative diseases, which are diseases that are typically fatal and without other robust therapies.
It has long been known that the pathologic hallmarks of AD (i.e., plaques and neurofibrillary tangles) are composed of beta-amyloid and tau protein aggregates. However, the pathogenic mechanisms that drive the association between these protein aggregates and the clinical symptoms are not known. A wide-array of global, molecular, and cellular processes have been hypothesized to play a role in AD pathogenies including network failure, pathologic plasticity, mitochondrial dysfunction, innate immunity, inflammation, autophagy, and toxicity of protein aggregates and oligomers like amyloid. The ability of MSCs to secrete neurotrophic factors may improve the cellular milieu and limit cell loss in the setting of this complex AD pathophysiology. In addition, MSCs’ known immunomodulatory effects may limit the damage effects of activated glial cell related synaptic pruning and inflammation in general. MSCs also have the potential to deliver a healthy supply of mitochondria to the CNS thereby mitigating the impact of age and AD-related mitochondrial dysfunction.
View the study: https://pmc.ncbi.nlm.nih.gov/articles/PMC6643282/
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. It is caused by synaptic failure and excessive accumulation of misfolded proteins. To date, almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD. Also, currently available drug candidates intervene too late. Stem cells have improved characteristics of self-renewal, proliferation, differentiation, and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells. Stem cell treatment has been successful in AD animal models. Recent preclinical studies on stem cell therapy for AD have proved to be promising. Cell replacement therapies, such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells, have the potential to treat patients with AD, and human clinical trials are ongoing in this regard. However, many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases. This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.
View the study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7477654/
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment. It is caused by synaptic failure and excessive accumulation of misfolded proteins. To date, almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD. Also, currently available drug candidates intervene too late. Stem cells have improved characteristics of self-renewal, proliferation, differentiation, and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells. Stem cell treatment has been successful in AD animal models. Recent preclinical studies on stem cell therapy for AD have proved to be promising. Cell replacement therapies, such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells, have the potential to treat patients with AD, and human clinical trials are ongoing in this regard. However, many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases. This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.
View the study: https://pmc.ncbi.nlm.nih.gov/articles/PMC7477654/
