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Journal of Neurodegenerative Disorders

ISSN: 2642-4274

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Review Article | VOLUME 5 | ISSUE 1 | DOI: 10.36959/459/608 OPEN ACCESS

Similarities among Alzheimer's Disease, Parkinson's Disease and Dementia may Call for a Similar Treatment

Ashok Chakraborty, PhD and Anil Diwan, PhD

  • Ashok Chakraborty 1*
  • Anil Diwan 1
  • AllExcel, Inc., CT, USA

Chakraborty A, Diwan A (2022) Similarities among Alzheimer's Disease, Parkinson's Disease and Dementia may Call for a Similar Treatment. J Neurodegener Disord 5(1):133-140.

Accepted: May 07, 2022 | Published Online: May 09, 2022

Similarities among Alzheimer's Disease, Parkinson's Disease and Dementia may Call for a Similar Treatment

Abstract

Alzheimer's Disease (AD), Parkinson's Disease (PD), and Dementia are all age-related neurodegenerative diseases. In the US, AD victims are increasing every year from 5.5 million in 2018 to 13.8 million by 2050. PD patient are calculated to increase from 7K to 1 million by 2030. Results from accumulation of extracellular amyloid-β (Aβ) peptide and deposition of intracellular tau aggregated tangles. The prognosis of AD and PD both is the onset of Dementia, which causes memory impairment irreversibly, thinking capabilities, orientation, comprehension, learning any new things, and taking the judgment. Dementia is currently the seventh leading cause of death among all diseases worldwide. Here we will discuss the similarities in the disease nature and cause of AD, PD and Dementia at their cellular and molecular level to find a common therapy for them (Graphical Abstract).

Keywords

Alzheimer's disease (AD), Parkinson's Disease (PD), Dementia, Tangles, Plaques, Cognitive function

Abbreviations

AD: Alzheimer's Disease; LOAD: Late-Onset AD, SPs: Senile Plaques; NMDA: N-methyl-D-aspartate; Aβ: Amyloid-Beta Peptide; EphB2 receptors: Ephrin type-B receptor 2; NFTs: Neurofibrillary Tangles; ApoE: Apolipoprotein E; pTau: Hyperphosphorylated tau; BACE1: β-site APP Cleaving Enzyme type-I; APP: Amyloid Precursor Protein; LTD: Long-term Depression; EOAD: Early-Onset AD; MTs: Microtubules; PSEN1 and PSEN2: Presenilins 1 and 2; ptau: Phosphorylated 'tau'; AICD: APP Intracellular Domain; Cdk-5: Cyclin-Dependent Kinase 5; sAPPβ: Soluble Ectodomain-β; cdc-2: Cell-Cycle Kinase; sAPPα: soluble Ectodomain-α; ROS: Reactive Oxygen Species

Introduction

The typical neurodegenerative diseases are Parkinson's disease (PD) and Alzheimer's disease (AD) and Dementia [1]. Both PD and AD display mitochondrial dysfunction and oxidative stress [2-4], while Dementia is a broad term that stands for an irreversible loss of thinking ability, memory, and other mental capabilities [5,6]. In fact, Dementiais considered as the end results of AD and PD. All these diseases are believed to be due to aging. This article will discuss the similarities and differences among these neural diseases and find for some appropriate treatment possibilities [7-75] (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6 and Table 7).

Conclusions

The greatest risk factor for AD, PD and Dementia is age. It appears thattau and Aβ are the hallmarks for both AD and PD in the brain and eventually for Dementia [76,77].

This review indicates large similarities in genetic risk factors between diseases, AD, PD and Dementia. The genes that were discussed above have the possibility as a potential biomarkers.

Using KEGG pathway analysis [78], Wang, et al. discovered that PD and AD were both dysfunctional in synaptic vesicle and mitochondrial oxidative metabolism pathways [79]. The enriched genes in AD cases was greater than PD. Although PD and AD have common characteristics [80]; cognition and patients with learning or memory damage in AD was more severe than in PD [81].

Epigenetic regulatory mechanisms, such as chromatin remodeling, DNA methylation, histone variant and histone post-translational modification have been suggested to regulate numerous aspects of axonal development and neuronal survival [82]. One study presented evidence that changes in H3K27ac or H3K4me3 occurred in connection with genetic variants in AD. This is an important function for immune-associated enhancers and promoter proteins in determining AD susceptibility [83]. Another study demonstrated that H4K16ac, a histone associated with DNA repair and neurodegenerative disorders, is significantly reduced in the cortex of AD patients. This suggests that the aged brains of these individuals are incapable of up-regulating H4K16ac [84]. In addition, multiple reports have associated loss of H3K4me3, a protein related to gene activation, with the deterioration found in PD. Overexpression of H3K4me3 can accelerate A-T mutation that mitigates behavioral impairments and neurodegeneration [85-87].

HDAC inhibitors can prevent neuro-degeneration in models of AD [88-91]. This paper demonstrate that epigenetic profiles are regulated in neurodegenerative diseases and gives a better understanding of these mechanisms that can provide the foundation for developing more precisely targeted epigenome therapies. For example, recent work suggesting that epigenetic editing can improve cognition in AD highlights the potential of epigenetic regulation-based gene therapy for neurodegenerative disorders [92].

Gene modification of stem cells prior to transplantation can be useful for increasing cell survival and making them more effective [93]. Due to the loss of cholinergic neurotransmitters in AD, gene-modified cells transplantation can produce acetylcholine (Ach) and could be beneficial to the patients. Primary fibroblast cell line genetically engineered to express choline acetyltransferase showed the capacity to produce Ach after transplantation into the hippocampus of rats [94]. Another example of the use of the facilitation of genetherapy for AD is the over expression of neprilysine (NEP), an Aβ degrading protease that has been shown to ameliorate extracellular amyloids [95].

Transgenic mice (APP/PS1) injected with lentiviral vector expressing NEP showed a reduction in Ab deposits [96], and MSCs overexpressing the NEP gene demonstrated the ability to degrade Aβ peptides in vitro [97]. Similar results were obtained in vivo with transgenic mice that were transplanted with fibroblasts engineered with lentivirus carrying NEP [98].

Recently we have created modified neural stem cells which can differentiate, produce dopamine, BDNF/GDNF [99-101]. Our notion, therefore, is that the cell-replacement therapy of AD/PD/Dementia patients with modified neural cells could be relevant [102-106].

Acknowledgments

We acknowledge all our colleagues for their help during the preparation of the manuscript by providing all the relevant information. Thanks to Ms. Bethany Pond for her Editorial assistants.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Authors' Contribution

Both the authors have contributed equally to preparing this article, reading, and approving the final manuscript.

Conflict of Interests

The authors declare no conflict of interests.

Consent for Publications

Both the authors have agreed to submit this paper for publication.

Ethical Approval

Not applicable.

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Corresponding Author

Ashok Chakraborty, PhD, Sr. Research Scientist, Allexcel, Inc., 1 Controls Drive, Shelton, CT 06484, USA.

© 2022 Chakraborty A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Alzheimer's Disease (AD), Parkinson's Disease (PD), and Dementia are all age-related neurodegenerative diseases. In the US, AD victims are increasing every year from 5.5 million in 2018 to 13.8 million by 2050. PD patient are calculated to increase from 7K to 1 million by 2030. Results from accumulation of extracellular amyloid-β (Aβ) peptide and deposition of intracellular tau aggregated tangles. The prognosis of AD and PD both is the onset of Dementia, which causes memory impairment irreversibly, thinking capabilities, orientation, comprehension, learning any new things, and taking the judgment. Dementia is currently the seventh leading cause of death among all diseases worldwide. Here we will discuss the similarities in the disease nature and cause of AD, PD and Dementia at their cellular and molecular level to find a common therapy for them (Graphical Abstract).

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