Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are progressive disorders characterized by the loss of neurons. These conditions share pathological properties, including abnormal protein aggregations, oxidative stress, neuroinflammation, and cellular dysfunction. While current treatments primarily aim to manage symptoms, recent advances in research have introduced novel therapeutic strategies, including neural stem cell (NSC) transplantation and the modulation of the microbiota–gut–brain axis, which offer promising methods.
Pathological Basis of Neurodegenerative Diseases
Neurodegenerative diseases are often classified based on their clinical presentation, affected brain regions, and underlying molecular pathology. For example, AD is primarily characterized by amyloid-beta (Aβ) plaques and tau protein tangles, while PD is marked by α-synuclein aggregation in Lewy bodies. ALS involves TDP-43 proteinopathy and motor neuron degeneration, whereas HD is associated with huntingtin protein misfolding.
Neural Stem Cell Transplantation
NSC transplantation is being explored as a potential treatment for neurodegenerative diseases due to its ability to replace lost neurons, modulate the immune response, and enhance neuroprotection. NSCs can be derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), and they have been shown to produce neurotrophic factors, reduce inflammation, and integrate into host neuronal circuits. Studies in animal models have demonstrated that NSC transplantation can restore motor function, improve cognitive abilities, and slow disease progression. However, challenges remain, including immune rejection, tumorigenic potential, and the need for standardized differentiation protocols.
The Microbiota–Gut–Brain Axis in Neurodegeneration
Recent research highlights the role of the microbiota–gut–brain axis in neurodegenerative diseases. The gut microbiota influences brain function through metabolic products such as short-chain fatty acids (SCFAs), neurotransmitters, and immune signaling molecules. Altered gut microbiota composition has been observed in patients with AD, PD, and ALS, suggesting its involvement in disease pathogenesis. For example, SCFAs can mitigate neuroinflammation by modulating microglial activation, whereas dysbiosis (microbial imbalance) can exacerbate neurodegeneration.
Microbiome-Based Therapeutic Interventions
Targeting the gut microbiome offers a novel approach for treating neurodegenerative diseases. Strategies include:
- Probiotics and Prebiotics: These can promote beneficial microbial populations and enhance gut–brain signaling.
- Fecal Microbiota Transplantation (FMT): Preliminary studies suggest that FMT may improve cognitive function and motor symptoms in neurodegenerative diseases
- Metabolite-Based Therapies: SCFA supplementation and other microbial-derived metabolites may offer neuroprotective effects.
Future Perspectives and Challenges
While NSC transplantation and microbiome-based interventions show potential, their clinical applications require further validation. NSC therapy necessitates standardized protocols, improved graft survival, and strategies to prevent immune rejection. Similarly, microbiome-targeted treatments require a deeper understanding of host–microbiome interactions and long-term safety assessments. Ongoing research and clinical trials will determine the viability of these approaches as disease-modifying therapies for neurodegenerative disorders.
Neurodegenerative diseases remain a major challenge in neurology, with limited therapeutic options. However, emerging approaches such as NSC transplantation and microbiome modulation offer new hope. As research advances, these strategies could pave the way for more effective and personalized treatments, ultimately improving patient outcomes and quality of life.
Sources
De Gioia, Roberta et al. “Neural Stem Cell Transplantation for Neurodegenerative Diseases.” International journal of molecular sciences vol. 21,9 3103. 28 Apr. 2020, doi:10.3390/ijms21093103
Loh, Jian Sheng et al. “Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.” Signal transduction and targeted therapy vol. 9,1 37. 16 Feb. 2024, doi:10.1038/s41392-024-01743-1
Dugger, Brittany N, and Dennis W Dickson. “Pathology of Neurodegenerative Diseases.” Cold Spring Harbor perspectives in biology vol. 9,7 a028035. 5 Jul. 2017, doi:10.1101/cshperspect.a028035
Genchi, Angela et al. “Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study.” Nature medicine vol. 29,1 (2023): 75-85. doi:10.1038/s41591-022-02097-3
Hayashi, Yoshihito et al. “Effects of neural stem cell transplantation in Alzheimer’s disease models.” Journal of biomedical science vol. 27,1 29. 27 Jan. 2020, doi:10.1186/s12929-020-0622-x
By. Hayoung Kim