Neurophysiology Research

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (629)348-3199

Mini Review - Neurophysiology Research (2022) Volume 4, Issue 4

A significant update on basic neurodegenerative mechanisms.

Andrey Abramov*

Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, Queen Square, UK

*Corresponding Author:
Andrey Abramov
Department of Molecular Neuroscience
UCL Institute of Neurology
University College London, Queen Square, UK
E-mail: aabramov@ucl.ac.uk

Received: 05-Aug-2022, Manuscript No. AANR-22-75726; Editor assigned: 06-Aug-2022, PreQC No. AANR-22-75726(p); Reviewed: 19-Aug-2022, QC No. AANR-22-75726; Revised: 23-Aug-2022, Manuscript No. AANR-22-75726(R); Published: 30-Aug-2022,DOI:10.35841/aanr-4.4.119

Citation: Abramov A. A significant update on basic neurodegenerative mechanisms. Neurophysiol Res. 2022;4(4):119

Visit for more related articles at Neurophysiology Research

Abstract

Clinical appearance of neurodegenerative disorders is determined by the increasing malfunctioning of particular populations of neurons. The characteristic of many neurodegenerative proteinopathies, extracellular and intracellular accumulation of misfolded proteins, is linked to neuronal death. Major fundamental processes include abnormal protein dynamics caused by ubiquitin-proteosome-autophagy system deficiencies, oxidative stress and free radical formation, mitochondrial dysfunction, compromised bioenergetics, dysfunction of neurotrophins, "neuroinflammatory" processes, and (secondary) disruptions of neuronal Golgi apparatus and axonal transport. These connected systems work together over many years to cause programmed cell death. The principal components of protein deposits or known genetic processes are used to categorise neurodegenerative illnesses, however new research have revealed overlap and intraindividual differences between various symptoms. Pathological proteins' synergistic interactions imply widespread pathogenic pathways. Animal models and other studies have shed light on the fundamental mechanisms underlying neurodegeneration and cell death, opening up fresh avenues for potential future prevention/treatment approaches.

Keywords

Neuroinflammatory, Neurodegeneration, Neuronal Golgi apparatus.

Introduction

A group of medical illnesses known as neurodegenerative disorders are caused by slow-moving, irreversible malfunction and loss of neurons and synapses in specific regions of the nervous system, which affects how they present clinically and how they proceed. The main fundamental mechanisms that induce neurodegeneration are thought to be complex and brought on by genetic, environmental, and endogenous aging-related factors; however, the pathogenic function and fundamental molecular mechanisms of these variables are not fully understood [1]. Currently, NDDs are categorised in accordance with the key chemical components of their protein deposits or known genetic pathways. These diseases are referred to be "protein misfolding" diseases or proteinopathies based on the crucial structural abnormalities that occur in proteins [2]. The toxic effects of early-phase products, such as soluble oligomers and protofibrillar derivatives of misfolded proteins, are thought to be the cause of the causative relationship between the production of protein aggregates and ND. The precise biochemical mechanisms, however, are not well understood [3]. The protein context of enlarged polyQ and its soluble mutant conformers is crucial for the disease specificity in polyQ disorders. While sporadic amyotrophic lateral sclerosis lacks evidence of monomer or misfolded SOD1, familial amyotrophic lateral sclerosis, which is linked to the two genes TARDBP and FUS, has structural and dynamic aspects related to oligomerization of superoxide dismutase 1 and its mutants that have provided better insight. SOD1, TARDBP, and FUS aggregate deposits are present in ALS, as they are in most NDDs. The variety of their biological functioning is widened by the discovery of new prions [4]. It also encourages the formation of filaments from these pathogenic conformers in the cytosol, nucleus, or extracellular space of afflicted brain cells in a disease- and protein-specific way. Discussions currently focus on the connection between A and PrPC as well as PrPC's function in the pathogenesis of AD. Protein aggregation, changes in CO2 homeostasis, and other significant pathogenic variables are present in spinocerebellar ataxia [5].

Conclusion

The pathophysiology of PD includes cell death significantly. The main contender for a hazardous protein, despite the mystery surrounding the process, is Syn and its aberrant variants, including increased expression of the normal gene. Although the chemical mechanisms that start dopaminergic neuron loss are unknown, apoptosis may have a role in Parkinson's Disease (PD). These include, among others, cellcycle reactivation, JNK signalling, p53 activation, and Bcl- 2 protein signalling. Whether PCD genuinely takes place in the human PD brain is still up for debate, and this notion has neither been definitively proven by many research nor rejected. It is still unclear if LBs and other Syn aggregates are cytotoxic or protective.

References

  1. Golde TE, Miller VM. Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases. Alzheimers Res Ther. 2009;1(2):1-2.

    2. Indexed at, Google Scholar, Cross ref

  2. Kovacs GG, Budka H. Protein-based neuropathology and molecular classification of human neurodegenerative diseases. InProtein folding and misfolding: neurodegenerative diseases 2009:251-272.

    3. Indexed at, Google Scholar, Cross ref

  3. Morris AM, Watzky MA, Finke RG. Protein aggregation kinetics, mechanism, and curve-fitting: a review of the literature. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2009 1;1794(3):375-97.

    4. Indexed at, Google Scholar, Cross ref

  4. Lafaye P, Achour I, England P, et al. Single-domain antibodies recognize selectively small oligomeric forms of amyloid β, prevent Aβ-induced neurotoxicity and inhibit fibril formation. Mol Immunol. 2009 1;46(4):695-704.

    5. Indexed at, Google Scholar, Cross ref

  5. Xia W, Yang T, Smith IM, et al. A specific ELISA for measuring amyloid β-protein oligomers in human plasma and the brains of Alzheimer patients. Arch Neurol. 2009;66(2):190.

    6. Indexed at, Google Scholar, Cross ref

Get the App