Proteotoxicity and Neurodegenerative Diseases

Ruz, Clara; Alcantud, Jose Luis; Montero, Francisco Vives; Durán, Raquel; Bandrés‐Ciga, Sara

doi:10.3390/ijms21165646

Cited by 48 publications

(38 citation statements)

References 201 publications

(142 reference statements)

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“…Moreover, AChE has a number of different functions beyond the breakdown of ACh, including participation in inflammation, cell apoptosis, morphogenic and adhesion functions, as well as participation in oxidative stress. During neurodegenerative diseases and depressive disorders, inflammation, cell apoptosis and increased oxidative stress occur [9]. AChE also plays a role in the theory of catecholaminergic-cholinergic balance in depressive disorders [10].…”

Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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Acetylcholinesterase (AChE) plays an important role in the pathogenesis of neurodegenerative diseases by influencing the inflammatory response, apoptosis, oxidative stress and aggregation of pathological proteins. There is a search for new compounds that can prevent the occurrence of neurodegenerative diseases and slow down their course. The aim of this review is to present the role of AChE in the pathomechanism of neurodegenerative diseases. In addition, this review aims to reveal the benefits of using AChE inhibitors to treat these diseases. The selected new AChE inhibitors were also assessed in terms of their potential use in the described disease entities. Designing and searching for new drugs targeting AChE may in the future allow the discovery of therapies that will be effective in the treatment of neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Walczak-Nowicka

Herbet

2021

IJMS

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“…In addition to cause intracellular Ca 2+ dysregulation, per se activating the apoptotic pathways, proteotoxicity lead to cellular dysfunction and death through other mechanisms (Ruz et al, 2020 ). For instance, PAO-induced toxicity can cause disruption of mitochondrial membrane integrity and ultimately lead to metabolic cellular dysfunctions (Mclendon and Robbins, 2015 ).…”

Section: Aggregates: Indexes Of Misfolding—origin and Consequences Inmentioning

confidence: 99%

The Heart of the Alzheimer's: A Mindful View of Heart Disease

2021

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Purpose of Review: This review summarizes the current evidence for the involvement of proteotoxicity and protein quality control systems defects in diseases of the central nervous and cardiovascular systems. Specifically, it presents the commonalities between the pathophysiology of protein misfolding diseases in the heart and the brain.Recent Findings: The involvement of protein homeostasis dysfunction has been for long time investigated and accepted as one of the leading pathophysiological causes of neurodegenerative diseases. In cardiovascular diseases instead the mechanistic focus had been on the primary role of Ca2+ dishomeostasis, myofilament dysfunction as well as extracellular fibrosis, whereas no attention was given to misfolding of proteins as a pathogenetic mechanism. Instead, in the recent years, several contributions have shown protein aggregates in failing hearts similar to the ones found in the brain and increasing evidence have highlighted the crucial importance that proteotoxicity exerts via pre-amyloidogenic species in cardiovascular diseases as well as the prominent role of the cellular response to misfolded protein accumulation. As a result, proteotoxicity, unfolding protein response (UPR), and ubiquitin-proteasome system (UPS) have recently been investigated as potential key pathogenic pathways and therapeutic targets for heart disease.Summary: Overall, the current knowledge summarized in this review describes how the misfolding process in the brain parallels in the heart. Understanding the folding and unfolding mechanisms involved early through studies in the heart will provide new knowledge for neurodegenerative proteinopathies and may prepare the stage for targeted and personalized interventions.

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“…Unfortunately, these goals have been reached merely for a minuscule fraction of diseases. The large majority of ailments-affecting from just a handful of patients to millions worldwide-awaits a treatment [1][2][3]. There are numerous reasons for the slow progress such as rare occurrence, molecular complexity, and variability of symptoms.…”

Section: Niemann-pick Type C Diseasementioning

confidence: 99%

Understanding and Treating Niemann–Pick Type C Disease: Models Matter

Pallottini

Pfrieger

2020

IJMS

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Biomedical research aims to understand the molecular mechanisms causing human diseases and to develop curative therapies. So far, these goals have been achieved for a small fraction of diseases, limiting factors being the availability, validity, and use of experimental models. Niemann–Pick type C (NPC) is a prime example for a disease that lacks a curative therapy despite substantial breakthroughs. This rare, fatal, and autosomal-recessive disorder is caused by defects in NPC1 or NPC2. These ubiquitously expressed proteins help cholesterol exit from the endosomal–lysosomal system. The dysfunction of either causes an aberrant accumulation of lipids with patients presenting a large range of disease onset, neurovisceral symptoms, and life span. Here, we note general aspects of experimental models, we describe the line-up used for NPC-related research and therapy development, and we provide an outlook on future topics.

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Proteotoxicity and Neurodegenerative Diseases

Cited by 48 publications

References 201 publications

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis

The Heart of the Alzheimer's: A Mindful View of Heart Disease

Understanding and Treating Niemann–Pick Type C Disease: Models Matter

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