The role and therapeutic implication of protein tyrosine phosphatases in Alzheimer’s disease

Zhao, Xia; Li, Xiong; She, Lingyu; Li, Liwei; Huang, Ping; Liang, Guang

doi:10.1016/j.biopha.2022.113188

Cited by 7 publications

(3 citation statements)

References 108 publications

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“…monoacylglycerol lipase [175]; NRLP3 Inflammasome [176]; PPAR [177]; TRPC5 [178] Neuroprotection Apoptosis [179]; ferroptosis [180]; sigma 1 and 2 receptors [181] Apoptosis [182];…”

Section: Mitochondria and Metabolic Functionsmentioning

confidence: 99%

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Sequeira,

Benfeito,

Fernandes

et al. 2024

Preprint

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Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

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“…monoacylglycerol lipase [175]; NRLP3 Inflammasome [176]; PPAR [177]; TRPC5 [178] Neuroprotection Apoptosis [179]; ferroptosis [180]; sigma 1 and 2 receptors [181] Apoptosis [182];…”

Section: Mitochondria and Metabolic Functionsmentioning

confidence: 99%

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Sequeira,

Benfeito,

Fernandes

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The C terminal folds on the microtubule-binding domain, and the N terminal folds back to the C terminal, forming the Tau "paperclip" conformation. [62] Excessive phosphorylation caused by the abnormal activity of protein kinase and phosphatase, [63][64] the "paperclip" conformation loosens and the tightens. This decreases the binding affinity of Tau to microtubules, leading to its dissociation from microtubules and accelerating normal cells' death.…”

Section: Tau Hypothesismentioning

confidence: 99%

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

Huang,

Liao,

et al. 2023

Adv Funct Materials

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Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease that constitutes the third most common cause of death among elderly individuals. AD patients suffer from behavioral problems regularly, like memory loss, thinking deficits, and cognitive disorders. Currently, the incidence rate of AD has been on the rise worldwide. Therefore, it is imperative to develop effective strategies for the treatment and prevention of AD. The inherent characteristics of low‐dimensional nanomaterials, primarily their smaller size and surface structure, make them well‐suited for fulfilling the essential requirements of therapeutic drug design. Consequently, these nanomaterials offer a highly appealing and alternative approach to treating AD. Here, the low‐dimensional nanomaterials used in the treatment of AD to provide new ideas, methods, and comprehensive perspectives for the management of AD are reviewed. This review will advance the comprehensive understanding of the potential of low‐dimensional nanomaterials in the field of neuro medicine, which also will have a positive impact on future research.

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“…Despite their greater abundance, PTPs have garnered less attention from researchers than PTKs. Nevertheless, it is known that dysfunction of PTPs can disrupt the homeostasis of tyrosine-phosphorylated proteins, contributing to a spectrum of disorders including cancers and neuronal and autoimmune diseases (4)(5)(6)(7)(8)(9). Notably, among the 237 protein phosphatases in C. elegans, 94 are presumed to be PTPs and over 50% of C. elegans phosphatases have human orthologs (10,11).…”

Section: Introductionmentioning

confidence: 99%

A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes inC. elegans

Binti,

Linder,

Edeen

et al. 2024

Preprint

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Protein tyrosine phosphatases non-receptor type (PTPNs) have been studied extensively in the context of the adaptive immune system; however, their roles beyond immunoregulation are less well explored. Here we identify novel functions for the conserved C. elegans phosphatase PTPN-22, establishing its role in nematode molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen, we found that loss of PTPN-22 phosphatase activity suppressed molting defects caused by loss-of-function mutations in the conserved NIMA-related kinases NEKL-2 (human NEK8/NEK9) and NEKL-3 (human NEK6/NEK7), which act at the interface of membrane trafficking and actin regulation. To better understand the functions of PTPN-22, we carried out proximity labeling studies to identify candidate interactors of PTPN-22 during development. Through this approach we identified the CDC42 guanine-nucleotide exchange factor DNBP-1 (human DNMBP) as an in vivo partner of PTPN-22. Consistent with this interaction, loss of DNBP-1 also suppressed nekl-associated molting defects. Genetic analysis, co-localization studies, and proximity labeling revealed roles for PTPN-22 in several epidermal adhesion complexes, including C. elegans hemidesmosomes, suggesting that PTPN-22 plays a broad role in maintaining the structural integrity of tissues. Localization and proximity labeling also implicated PTPN-22 in functions connected to nucleocytoplasmic transport and mRNA regulation, particularly within the germline, as nearly one-third of proteins identified by PTPN-22 proximity labeling are known P granule components. Collectively, these studies highlight the utility of combined genetic and proteomic approaches for identifying novel gene functions.

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The role and therapeutic implication of protein tyrosine phosphatases in Alzheimer’s disease

Cited by 7 publications

References 108 publications

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes inC. elegans

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