Demise\'s Echo: Exploring Cell Death in Neurodegeneration

Enzo Gabriel^*
*Correspondence: Enzo Gabriel, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK, Email:

Introduction

Neurodegeneration is a complex process characterized by the progressive loss of structure or function of neurons, leading to cognitive decline and motor dysfunction. One of the hallmark features of neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's is the occurrence of cell death within the central nervous system. Understanding the mechanisms underlying cell death in neurodegeneration is crucial for developing effective therapeutic strategies. In this article, we delve into the various forms of cell death implicated in neurodegenerative disorders and explore the intricate molecular pathways involved.

Description

Apoptosis, often referred to as programmed cell death, is a tightly regulated process essential for maintaining tissue homeostasis and eliminating damaged or unnecessary cells. In the context of neurodegeneration, dysregulation of apoptotic pathways can contribute to neuronal loss. Aberrant accumulation of misfolded proteins, oxidative stress and mitochondrial dysfunction are common triggers of apoptosis in neurodegenerative diseases. For instance, in Alzheimer's disease, the aggregation of amyloid-beta peptides and hyperphosphorylated tau proteins can initiate apoptotic cascades, leading to synaptic dysfunction and neuronal death [1].

Autophagy is a cellular mechanism involved in the degradation and recycling of damaged organelles and proteins. Dysfunctional autophagy has been implicated in the pathogenesis of several neurodegenerative disorders. Impaired autophagic flux can lead to the accumulation of protein aggregates and neurotoxic substances, exacerbating neuronal damage. Conversely, excessive autophagy activation may trigger non-apoptotic cell death pathways. Modulating autophagy flux represents a promising therapeutic approach for mitigating neurodegeneration-associated cellular demise [2].

Necrosis, traditionally viewed as a chaotic and unregulated form of cell death, has gained recognition as a contributor to neurodegenerative processes. Unlike apoptosis, necrosis is characterized by cellular swelling, plasma membrane rupture and inflammatory responses. In conditions of severe oxidative stress or excitotoxicity, neurons may undergo necrotic death, releasing danger signals that propagate neuroinflammation and exacerbate tissue damage. Necrotic cell death has been implicated in various neurodegenerative disorders, including ischemic stroke, traumatic brain injury and multiple sclerosis.

Pyroptosis is a highly inflammatory form of programmed cell death triggered by activation of the inflammasome, a multiprotein complex sensing microbial infections and cellular damage. In the context of neurodegeneration, pyroptosis contributes to neuroinflammation and exacerbates neuronal injury. Inflammatory cytokines released during pyroptotic cell death can recruit immune cells and perpetuate neurotoxic cascades. Emerging evidence suggests a role for pyroptosis in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, highlighting its potential as a therapeutic target for attenuating neuroinflammation [3].

Excitotoxicity refers to neuronal damage caused by excessive stimulation of glutamate receptors, particularly N-methyl-D-aspartate (NMDA) receptors. Prolonged activation of NMDA receptors leads to calcium overload, mitochondrial dysfunction and activation of apoptotic and necrotic pathways. Excitotoxicity is implicated in various acute and chronic neurodegenerative conditions, including stroke, epilepsy and Huntington's disease. Targeting glutamate receptors and downstream signaling pathways holds promise for mitigating excitotoxic neuronal death and preserving neurological function.

Exploring Cell Death in Neurodegeneration" delves into the intricate relationship between cell death and neurodegenerative diseases. Within the realms of conditions like Alzheimer's, Parkinson's and Huntington's disease, understanding the mechanisms behind cell demise is pivotal for developing effective therapeutic strategies [4].

The discussion within this exploration likely touches upon various forms of cell death, including apoptosis, necrosis and autophagy-mediated cell death and how they intersect with the pathogenesis of neurodegenerative disorders. Apoptosis, often referred to as programmed cell death, plays a significant role in the progression of these diseases, as aberrant regulation of this process can lead to excessive neuronal loss.

Moreover, the discussion may highlight the role of neuroinflammation and oxidative stress in exacerbating cell death pathways, creating a vicious cycle of neuronal damage. Understanding the intricate molecular mechanisms driving these processes could unveil potential targets for therapeutic intervention [5].

Furthermore, exploring the interplay between cell death and protein aggregation, a hallmark feature of many neurodegenerative diseases, is crucial. Misfolded proteins, such as amyloid-beta and alpha-synuclein, can induce cytotoxicity and trigger cascades leading to neuronal demise.

Conclusion

Cell death is a multifaceted phenomenon intricately intertwined with the pathophysiology of neurodegenerative diseases. Apoptosis, autophagy, necrosis, pyroptosis and excitotoxicity represent diverse mechanisms through which neurons succumb to demise in neurodegeneration. Elucidating the molecular underpinnings of these cell death pathways is crucial for developing targeted therapeutic interventions aimed at preserving neuronal viability and ameliorating disease progression. Future research endeavors should focus on unraveling the intricate interplay between cell death mechanisms and identifying novel druggable targets for combating neurodegenerative disorders.

Acknowledgement

None.

Conflict of Interest

The authors declare no conflicts of interest.

References

1. Teng, Yang D and Ross D. Zafonte. "Prelude to the special issue on novel neurocircuit, cellular and molecular targets for developing functional rehabilitation therapies of neurotrauma." Exp Neurol 341 (2021): 113689.

   Google Scholar, Crossref, Indexed at

2. Tashiro, Syoichi, Masaya Nakamura and Hideyuki Okano. "The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models." Neural Regen Res 12 (2017): 43-46.

   Google Scholar, Crossref, Indexed at

3. Wessels, Monique, Cees Lucas, Inge Eriks and Sonja De Groot. "Body weight-supported gait training for restoration of walking in people with an incomplete spinal cord injury: A systematic review." J Rehabil Med 42 (2010): 513-519.

   Google Scholar, Crossref, Indexed at

4. Okawara, Hiroki, Syoichi Tashiro, Tomonori Sawada and Keiko Sugai, et al. "Neurorehabilitation using a voluntary driven exoskeletal robot improves trunk function in patients with chronic spinal cord injury: a single-arm study." Neural Regen Res 17 (2022): 427-432.

   Google Scholar, Crossref, Indexed at

5. Patil, Siddeshwar, Wajid A. Raza, Firas Jamil and Richard Caley, et al. "Functional electrical stimulation for the upper limb in tetraplegic spinal cord injury: A systematic review." J Med Eng Technol 39 (2015): 419-423.

   Google Scholar, Crossref, Indexed at