Introduction
Neurodegenerative diseases encompass a group of disorders characterized by neuronal loss and progressive degeneration of the nervous system, posing a significant global health challenge with increasing incidence rates (Sumera et al., 2023).
These diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis (ALS), and Multiple sclerosis, are multifactorial conditions often associated with gene mutations leading to protein dysfunction (Neelam et al., 2023).
Therapeutic interventions for these diseases include immune-suppressors, gene transfer therapy, and nanomedicines, showing promise in treating neurodegenerative disorders. Despite ongoing research efforts, effective therapeutics to slow or prevent neurodegenerative diseases are still lacking, emphasizing the critical need for further understanding of their molecular mechanisms and risk factors.
ALS (Amyotrophic Lateral Sclerosis)
Definition and Epidemiology
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a rare neurodegenerative disorder affecting upper and lower motor neurons, leading to progressive muscle weakness and paralysis. Epidemiological studies have highlighted the global variation in the incidence and prevalence of ALS, ranging from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan for incidence, and from 1.57 per 100,000 in Iran to 42.1 per 100,000 in Canada for prevalence (Emmanuelle et al., 2023).
Genetic factors, environmental influences, and lifestyle choices are believed to contribute significantly to the occurrence of ALS, with population-based disease registries playing a crucial role in advancing our understanding of the disease, including genotype-phenotype correlations and the identification of new genetic modifiers. International collaboration in epidemiological research is essential to fill the gaps in ALS data, especially in regions with limited information.
Pathophysiology
Amyotrophic Lateral Sclerosis (ALS) is characterized by the involvement of upper and lower motor neurons, with TDP-43 mislocalization and aggregation playing a key role in its pathogenesis (Mari and Yoshida (2019). Neuroinflammation, oxidative stress, and mitochondrial dysfunction contribute to neurodegeneration and motor neuron death in ALS, highlighting the complex interplay of various cell types in the disease progression (Mehdi et al., 2019).
Magnetic resonance imaging (MRI) has shown promise in detecting ALS pathology and tracking disease progression, with histological validation being crucial for understanding the MRI signal changes in post mortem brains.
Recent Discoveries and Advances
Recent advances in the study of Amyotrophic Lateral Sclerosis (ALS) have highlighted the role of extracellular vesicles (EVs) in the disease’s etiopathology, offering potential new therapeutic strategies (Gonçalo et al., 2023). Genetic research has identified over 40 ALS-related genes, aiding in a better understanding of the disease and the development of improved treatments (Hui et al., 2023).
Technological advancements, such as next-generation sequencing methods and long-read sequencing, have been crucial in uncovering new ALS-linked genes and understanding the complex genetics of ALS (Evan et al., 2023). Furthermore, the evolution of gene editing tools and the application of CRISPR/Cas9 have led to the creation of efficient animal models for ALS research, offering promising avenues for novel therapeutic approaches (Yajun et al., 2023).
These interdisciplinary efforts are shaping the landscape of ALS research, providing hope for improved diagnostics, treatments, and ultimately, better outcomes for patients.
Dementia
Types of Dementia and Prevalence
Dementia, a prevalent neurodegenerative disorder, encompasses various types such as Alzheimer’s disease, vascular dementia, and frontotemporal dementia, among others. The prevalence of dementia varies by geographic region, age, and gender, with higher rates in Europe and North America compared to Asia, Africa, and South America (Qing et al., 2020).
Studies show that the number of individuals living with dementia increases significantly with age, doubling approximately every five years, and is notably higher in women than in men [5]. By 2024, the UK is projected to have over 1.14 million people living with dementia, a number expected to rise to 2.09 million by 2051 due to population aging.
Despite extensive research efforts, no definitive cure for dementia has been identified, but advancements in understanding its pathogenesis offer hope for improved preventive and therapeutic strategies in the future.
Recent Research Progress
Recent research progress in dementia in 2024 has highlighted the importance of early identification and personalized management for young-onset dementia (YOD), emphasizing the need for age-specific care and integration with various health services (Samantha et al., 2022).
Despite significant advancements in biomarker identification for Alzheimer’s disease, translating these findings into improved patient care remains a challenge, with a large percentage of individuals not receiving post-diagnosis care. The global burden of dementia is substantial, with prevalence expected to rise significantly by 2030, necessitating a more inclusive approach to research and increased funding to effectively tackle this public health challenge (Lancet, 2023).
The recognition of the diagnostic and phenotypic complexity of YOD, along with the potential of biomarkers in early detection, underscores the ongoing efforts to enhance understanding and management of dementia in younger individuals.
Myasthenia Gravis
Overview of Myasthenia Gravis
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by autoantibodies targeting proteins at the neuromuscular junction, notably the nicotinic acetylcholine receptor (AChR) and muscle-specific kinase (MuSK)(Rebecca and Probert, 2023).
The pathophysiology involves autoreactive B cells producing antibodies regulated by T-cell signaling, leading to impaired antigen function, target protein removal, and complement-mediated destruction of the postsynaptic membrane (Gianvito et al., 2022). Clinical manifestations range from ocular muscle weakness causing double vision and ptosis to severe generalized weakness requiring mechanical ventilation .
Recent research has highlighted the diverse mechanisms of immunopathology between AChR and MuSK MG subtypes, influencing therapeutic responses and emphasizing the need for tailored treatments based on individual autoantibody profiles. Understanding these immunological mechanisms is crucial for developing specific and effective therapies for MG patients.
Recent Research Highlights
Recent research on myasthenia gravis (MG) has provided valuable insights into various aspects of the disease. Studies have identified risk factors for recurrent infection-triggered MG crises, including concomitant diabetes mellitus, hypomagnesemia, and prolonged activated partial thromboplastin time (Chia-Yin et al., 2023).
Technological advancements in machine learning have aided in accurate diagnosis and management of MG, while lifestyle changes like physical exercise and traditional Chinese medicine have shown positive effects on disease progression (Huang et al., 2022). Additionally, recent investigations have shed light on the immunopathogenesis of MG, highlighting differences in clinical responses between acetylcholine receptor and muscle-specific tyrosine kinase MG subtypes, and the need for individually tailored therapies based on immunological heterogeneity among patients (Hiroyuki and Murai, 2023). These findings underscore the evolving landscape of MG research and the importance of personalized approaches in its management.
Alzheimer’s Disease
Alzheimer’s disease (AD) is a prevalent form of dementia characterized by beta-amyloid plaques and neurofibrillary tangles in the brain, leading to neuronal damage and cognitive decline (Fikri et al., 2022). The diagnosis of AD traditionally relied on post-mortem neuropathology, but modern methods utilize biomarker imaging and fluid tests for more accurate detection.
Genetic factors like mutations in PSEN1, PSEN2, and APP genes, as well as non-genetic factors such as advanced age and lifestyle characteristics, contribute to the disease’s etiopathogenesis. The pathological hallmarks of AD include extracellular amyloid plaques and intraneuronal tau aggregates, with additional co-pathologies like cerebrovascular lesions and Lewy bodies influencing disease progression and clinical presentation.
Despite current therapies focusing on symptomatic relief, ongoing research targets disease-modifying treatments like anti-beta-amyloid and APOE-related therapies for more effective management of AD
Recent Breakthroughs in Alzheimer’s Research
Recent breakthroughs in Alzheimer’s research have focused on innovative pathways involving neural and peripheral inflammation, neuro-regeneration, and the blood-brain barrier (Allison et al., 2023).
While current treatments offer only symptomatic relief, new approaches target early AD stages to preserve cognitive function and neuronal viability (None et al., 2023). Studies have explored inhibiting microglial receptors, enhanced autophagy, and modulating the microbiome-brain-gut axis as potential strategies (Carlos et al., 2023). Nanoparticles are being investigated for improved drug delivery to the central nervous system, overcoming barriers like the blood-brain interface (Rima et al., 2022).
Clinical trials have shown promising results with anti-neuroinflammation drugs, anti-Aβ vaccines, and BACE inhibitors, offering hope for future AD therapies. Additionally, epigenetic factors and network biology approaches are emerging as valuable tools for understanding AD pathogenesis and identifying novel biomarkers and drug targets.
Huntington’s Disease
Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene, leading to the production of a mutated HTT protein that aggregates in various neuronal compartments, resulting in neuronal dysfunction and death (Anamaria and Jurcau, 2022).
The disease primarily affects the striatum but is considered a brain-wide disorder due to atrophy in multiple brain regions (Yi et al., 2022). HD manifests with motor symptoms like chorea, cognitive decline, and psychiatric disturbances, with earlier onset and increased severity correlating with higher CAG repeat lengths. Pathogenic mechanisms include excitotoxicity, mitochondrial dysfunction, oxidative stress, impaired proteostasis, altered axonal trafficking, and reduced trophic factor availability, contributing to neuronal demise. Research aims to understand these cascades to develop therapies that delay onset and slow disease progression.
Recent Advances in Huntington’s Disease Research
Recent advances in Huntington’s disease (HD) research have focused on various fronts. Studies have delved into the molecular basis of HD, emphasizing the trinucleotide expansion in the huntingtin gene and its implications on neurodegeneration (Anastasia-Marina et al., 2022).
Biochemical tools have been developed to better understand the interactions of the huntingtin protein with binding partners, aiding in uncovering disease mechanisms and potential therapeutic targets (Matthew et al., 2022). Gene therapy approaches, such as antisense oligonucleotides and zinc finger proteins, have shown promise in clinical trials, although challenges like side effects need to be addressed for effective treatment.
Cognitive dynamics in HD patients have been studied, revealing differences in impulse control dynamics and highlighting the need for further research to correlate these findings with clinical symptoms (Shuhei et al., 2023). Additionally, advanced cellular therapy utilizing mesenchymal stem cells and their exosomes has emerged as a potential avenue for neuroprotection and neuroregeneration in HD treatment, offering a novel approach to modifying the disease’s progression.
Common Pathogenic Mechanisms Across Neurodegenerative Diseases
In 2024, research indicates that neurodegenerative diseases, including Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, Huntington’s, and multiple sclerosis, share common pathogenic mechanisms such as protein misfolding, aggregation, and deposition, leading to the progressive impairment of the central nervous system (Alexander et al., 2019).
These diseases exhibit overlapping features like abnormal protein accumulation, dysfunctional cellular transport, mitochondrial deficits, inflammation, and iron accumulation, suggesting converging pathways of neurodegeneration (Lijun et al., 2014). Studies have identified shared genetic correlations and molecular pathophysiology between psychiatric and neurodegenerative disorders, emphasizing the importance of understanding these commonalities for early treatment and therapeutic development.
Furthermore, the transfer of disease-related proteins like alpha-synuclein, Tau, and huntingtin between cells through extracellular vesicles has been proposed as a potential mechanism contributing to disease progression, highlighting the significance of intercellular communication in neurodegenerative processes.
Precision Medicine Approaches
In 2024, precision medicine approaches are pivotal in addressing the challenges posed by neurodegenerative diseases, aiming to tailor interventions for individual patients based on genetic, epigenetic, and environmental factors (Sharyn et al., 2023).
The advancement of biomedical research and informatics has enabled a deeper understanding of disease mechanisms, emphasizing the importance of collaborative networks among medical centers and research institutes for the successful implementation of precision medicine strategies (Anjana et al., 2018). Neuroimaging techniques play a crucial role in observing disease manifestations and guiding personalized therapeutic strategies, particularly in conditions like Parkinson’s disease and epilepsy [5].
The future of neurodegenerative disease management lies in precision medicine-guided diagnoses, prevention, and treatment, emphasizing individualized evaluation and multidimensional information integration for tailored therapeutic approaches. Efforts are underway to overcome disease heterogeneity and translate precision medicine principles into effective disease-modifying treatments for neurodegenerative disorders in the coming years.
Integration of Basic Science and Clinical Research
In 2024, the integration of basic science and clinical research across neurodegenerative diseases continues to be a crucial focus, as highlighted in various research papers. The collaboration between disciplines and institutions is emphasized to explore shared mechanisms underlying different neurodegenerative diseases, leading to collective efforts in developing disease-modifying therapies for conditions like Alzheimer’s Dementia (AD) and Parkinson’s Disease (PD)(Sheng-Di et al., 2012).
Studies emphasize the importance of understanding protein interactions, pathological proteins, and their interactors to identify potential therapeutic targets, utilizing data integration and interactive visualizations to illuminate disease-related protein-protein interactions (Rex, 2004).
The establishment of platforms like the Neurodegenerative Disease Atlas (NDAtlas) provides a comprehensive view of protein interactions and alternative splicing impacts on disease-related networks, aiding in the identification of regulatory modules and potential treatment avenues.
Conclusion
In conclusion, neurodegenerative diseases such as ALS, dementia, myasthenia gravis, Alzheimer’s, and Huntington’s present significant global health challenges due to their complex etiologies and lack of definitive cures. Despite promising advances in genetic research, biomarker identification, and novel therapeutic strategies, effective treatments to halt or reverse these conditions remain elusive. Ongoing interdisciplinary efforts and international collaborations are crucial for improving our understanding of the molecular mechanisms and risk factors involved. Ultimately, precision medicine approaches and innovative research hold the potential to significantly improve patient outcomes and quality of life.
Reference
Emmanuelle, Perez, Tisserant. (2022). The challenge of amyotrophic lateral sclerosis descriptive epidemiology: to estimate low incidence rates across complex phenotypes in different geographic areas. Current Opinion in Neurology, 35(5):678-685. doi: 10.1097/wco.0000000000001097
Mari, Yoshida. (2019). Neuropathology of Amyotrophic Lateral Sclerosis. Brain and nerve, 71(11):1152-1168. doi: 10.11477/MF.1416201426
Mehdi, van, den, Bos., Nimeshan, Geevasinga., Mana, Higashihara., Parvathi, Menon., Steve, Vucic. (2019). Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques.. International Journal of Molecular Sciences, 20(11):2818-. doi: 10.3390/IJMS20112818
Neelam, R., Yadav., Dr., Rupali, Tasgaonkar. (2023). Neurodegenerative Disorder. International Journal For Science Technology And Engineering, 11(4):824-828. doi: 10.22214/ijraset.2023.500321
Sumera, Zaib., Hira, Javed., Imtiaz, Khan., Fadi, Jaber., Ali, Sohail., Zainab, Zaib., Tooba, Mehboob., N., Tabassam., Hanan, A., Ogaly. (2023). Neurodegenerative Diseases: Their Onset, Epidemiology, Causes and Treatment. Chemistryselect, 8(20) doi: 10.1002/slct.202300225
Gonçalo, Afonso., Jorge, Valero., Sandra, I., Mota., Elisabete, Ferreiro. (2023). Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives. Cells, 12(13):1763-1763. doi: 10.3390/cells12131763
Hui, Wang., Liping, Guan., Min, Deng. (2023). Recent progress of the genetics of amyotrophic lateral sclerosis and challenges of gene therapy. Frontiers in neuroscience, 17 doi: 10.3389/fnins.2023.1170996
Evan, Udine., Angita, Jain., Marka, van, Blitterswijk. (2023). Advances in sequencing technologies for amyotrophic lateral sclerosis research. Molecular Neurodegeneration, 18(1) doi: 10.1186/s13024-022-00593-1
Yajun, Shi., Yan, Zhao., Likui, Lu., Qinqin, Gao., Dong, Yeol, Yu., Miao, Sun. (2023). CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis. Frontiers in neuroscience, 17 doi: 10.3389/fnins.2023.1223777
Qing, Cao., Chen-Chen, Tan., Wei, Xu., Hao, Hu., Xi-Peng, Cao., Qiang, Dong., Lan, Tan., Jin-Tai, Yu. (2020). The Prevalence of Dementia: A Systematic Review and Meta-Analysis.. Journal of Alzheimer’s Disease, 73(3):1157-1166. doi: 10.3233/JAD-191092
Agueda, Rostagno. (2022). Pathogenesis of Alzheimer’s Disease. International Journal of Molecular Sciences, 24(1):107-107. doi: 10.3390/ijms24010107
Samantha, M, Loi., Yolande, A.L., Pijnenburg., Dennis, Velakoulis. (2022). Recent research advances in young-onset dementia. Current Opinion in Psychiatry, 36:126-133. doi: 10.1097/YCO.0000000000000843
The, Lancet, Neurology. (2023). Increasing diversity in dementia research.. Lancet Neurology, 22 1(1):1. doi: 10.1016/s1474-4422(22)00487-2
Rebecca, Probert. (2023). Ocular Myasthenia Gravis: A Current Overview. Eye and brain, Volume 15:1-13. doi: 10.2147/eb.s389629
Gianvito, Masi., Kevin, C., O’Connor. (2022). Novel pathophysiological insights in autoimmune myasthenia gravis. Current Opinion in Neurology, 35:586-596. doi: 10.1097/WCO.0000000000001088
Chia-Yin, Chien., Chun-Wei, Chang., Ming-Feng, Liao., Chun-Che, Chu., Long-Sun, Ro., Yih, Ru, Wu., Kuo-Hsuan, Chang., Chiung, Mei, Chen., Hung-Chou, Kuo. (2023). Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study. BMC Neurology, 23(1) doi: 10.1186/s12883-023-03306-3
Huang E, J-C., Meng, Huang, Wu., Tsung, Jen, Wang., Tsung-Jen, Huang., Yanrong, Li., Ching, Yu, Lee. (2022). Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions.. Aging and Disease, 0-0. doi: 10.14336/ad.2022.1215
Hiroyuki, Murai. (2023). Development of clinical research on myasthenia gravis: Present and prospective view from Japan. Clinical and Experimental Neuroimmunology, 14(1):4-4. doi: 10.1111/cen3.12740
Fikri, Erdemci., Firat, Asir., Fatih, Tas. (2022). Etiology and Histopathology of Alzheimer’s Disease and Current Approaches. Black sea journal of health science, 5(2):322-327. doi: 10.19127/bshealthscience.1064168
Allison, B., Reiss., Dalia, Muhieddine., Berlin, Jacob., Michael, C., Mesbah., Aaron, Pinkhasov., Irving, H., Gomolin., Mark, M., Stecker., Thomas, Wisniewski., Joshua, De, Leon.
None, Mohamed, Abd, Alsamieh. (2023). Recent Progress in the Treatment Strategies for Alzheimer’s Disease. Neuromethods, 3-47. doi: 10.1007/978-1-0716-3311-3_1
Carlos, Elias, Conti, Filho., Lairane, Bridi, Loss., Clairton, Marcolongo-Pereira., Joamyr, Victor, Rossoni, Júnior., Rafael, Mazioli, Barcelos., Orlando, Chiarelli-Neto., Bruno, Spalenza, da, Silva., Roberta, Passamani, Ambrosio., Fernanda, Cristina, de, Abreu, Quintela, Castro., Sarah, Fernandes, Teixeira., Nathana, J., Mezzomo. (2023). Advances in Alzheimer’s disease’s pharmacological treatment. Frontiers in Pharmacology, 14 doi: 10.3389/fphar.2023.1101452
Rima, Hajjo., Dima, A., Sabbah., Osama, H., Abusara., Abdel, Qader, Al, Bawab. (2022). A Review of the Recent Advances in Alzheimer’s Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics. Diagnostics, 12(12):2975-2975. doi: 10.3390/diagnostics12122975
Anamaria, Jurcau. (2022). Molecular Pathophysiological Mechanisms in Huntington’s Disease. Advances in Cardiovascular Diseases, 10(6):1432-1432. doi: 10.3390/biomedicines10061432
Yi, Shen., Yu, Tang. (2022). Analysis of the Epigenetic Mechanism and Treatment of Huntington’s Disease. Proceedings of Anticancer Research, 6(6):21-28. doi: 10.26689/par.v6i6.4512
Anastasia-Marina, Palaiogeorgou., Eleni, Papakonstantinou., Rebecca, Golfinopoulou., Markezina, Sigala., Thanasis, Mitsis., Louis, Papageorgiou., Io, Diakou., Katerina, Pierouli., Konstantina, Dragoumani., Demetrios, A., Spandidos., Flora, Bacopoulou., George, P., Chrousos., Elias, Eliopoulos., Dimitrios, Vlachakis. (2022). Recent approaches on Huntington’s disease (Review). Biomedical Reports, 18(1) doi: 10.3892/br.2022.1587
Matthew, G., Alteen., Justin, C., Deme., Claudia, P., Alvarez., Peter, Loppnau., Ashley, Hutchinson., Alma, Seitova., Renu, Chandrasekaran., Eduardo, Silva, Ramos., Christopher, Secker., Mona, Alqazzaz., Erich, E., Wanker., Susan, M., Lea., Cheryl, H., Arrowsmith., Rachel, Harding. (2022). Expanding the Huntington’s disease research toolbox; validated subdomain protein constructs for biochemical and structural investigation of huntingtin. bioRxiv, doi: 10.1101/2022.11.21.516512
Shuhei, Shiino., Nelleke, C., van, Wouwe., Scott, A., Wylie., Daniel, O., Claassen., Katherine, E, McDonell. (2023). Huntington disease exacerbates action impulses. Frontiers in Psychology, 14 doi: 10.3389/fpsyg.2023.1186465
Alexander, P., Marsh., Alexander, P., Marsh. (2019). Molecular mechanisms of proteinopathies across neurodegenerative disease: a review. 1(1):1-7. doi: 10.1186/S42466-019-0039-8
Lijun, Bai., Lin, Ai., Mingzhou, Ding., Yong, He., Lixing, Lao., Fanrong, Liang. (2014). Imaging Neurodegenerative Diseases: Mechanisms and Interventions. BioMed Research International, 2014:419317-419317. doi: 10.1155/2014/419317
Sharyn, L., Rossi., Preeti, Subramanian., Diane, E., Bovenkamp. (2023). The future is precision medicine-guided diagnoses, preventions and treatments for neurodegenerative diseases. Frontiers in Aging Neuroscience, 15 doi: 10.3389/fnagi.2023.1128619
Anjana, Munshi., Vandana, Sharma., Sulena, Singh. (2018). Precision medicine in stroke and other related neurological diseases. 235-241. doi: 10.1201/9781315154749-12
Sheng-Di, Chen., Jialin, C., Zheng. (2012). Translational Neurodegeneration, a platform to share knowledge and experience in translational study of neurodegenerative diseases. Translational neurodegeneration, 1(1):1-3. doi: 10.1186/2047-9158-1-1
Rex D, A, B, (2014). Selenium enriched mushrooms as a food supplement for prevention of neurodegenerative diseases. International Journal of Pharmacy and Pharmaceutical Sciences, 6(10):1-2.