Protein-protein interactions underlying the behavioral and psychological symptoms of dementia (BPSD) and Alzheimer’s disease

Mao, Yimin; Fisher, Daniel; Yang, Shuxing; Keszycki, Rachel; Dong, Hongxin

doi:10.1371/journal.pone.0226021

Cited by 15 publications

(12 citation statements)

References 164 publications

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“…The atrophy of the amygdala was more serious in AD patients with mental symptoms in this study, consistent with previous studies[ 16 ]. About 80%-90% of patients with AD experience at least one kind of psychobehavioral symptoms, such as anxiety, agitation, irritability, aggression, disinhibition, depression, apathy, which can reduce the quality of life of patients and increase the burden of care[ 25 - 28 ]. The amygdala is attached to the terminal part of the hippocampus and is associated with multiple brain regions to regulate multiple stages of memory formation[ 1 , 2 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

Wang¹,

Ding²,

Bian³

et al. 2021

WJCC

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BACKGROUND The main clinical manifestation of Alzheimer’s disease (AD) is memory loss, which can be accompanied by neuropsychiatric symptoms at different stages of the disease. Amygdala is closely related to emotion and memory. AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging (sMRI) for AD. METHODS In this study, 22 patients with AD and 26 controls were enrolled. Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software. RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes. Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8% and 88.5%, respectively. Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms, which mainly included irritability (22.73%), sleep difficulties (22.73%), apathy (18.18%), and hallucination (13.64%). CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD, and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.

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Section: Discussionmentioning

confidence: 99%

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

Wang¹,

Ding²,

Bian³

et al. 2021

WJCC

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“…[3][4][5][6][7] PPIs play vital roles in various cellular processes, including many important diseases such as various cancers 7 and Alzheimer's disease. 8 As a PPI is formed by two or more proteins, the total number of PPIs (interactome) is much larger than the individual human protein target space, which is estimated to be around 19,000. 9 The Center for Cancer Systems Biology (CCSB) Interactome Database contains 13,993 human PPIs, 10 and 3,787 viral protein-human protein interactions, 11 which were determined by experiments.…”

Section: Introductionmentioning

confidence: 99%

“… 3–7 PPIs play vital roles in various cellular processes, including many important diseases such as various cancers 7 and Alzheimer’s disease. 8 …”

Section: Introductionmentioning

confidence: 99%

<p>Current Challenges and Opportunities in Designing Protein–Protein Interaction Targeted Drugs</p>

Shin

Kumazawa

Imai

et al. 2020

AABC

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It has been noticed that the efficiency of drug development has been decreasing in the past few decades. To overcome the situation, protein–protein interactions (PPIs) have been identified as new drug targets as early as 2000. PPIs are more abundant in human cells than single proteins and play numerous important roles in cellular processes including diseases. However, PPIs have very different physicochemical features from the conventional drug targets, which make targeting PPIs challenging. Therefore, as of now, only a small number of PPI inhibitors have been approved or progressed to a stage of clinical trial. In this article, we first overview previous works that analyzed differences between PPIs with PPI targeting ligands and conventional drugs with their binding pockets. Then, we constructed an up-to-date list of PPI targeting drugs that have been approved or are currently under clinical trial and have bound drug–target structures available. Using the dataset, we analyzed the PPIs and their ligands using several scores of druggability. Druggability scores showed that PPI sites and their drugs targeting PPIs are less druggable than conventional binding pockets and drugs, which also indicates that PPI drugs do not follow the conventional rules for drug design, such as Lipinski’s rule of five. Our analyses suggest that developing a new rule would be beneficial for guiding PPI-drug discovery.

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“…Protein-protein association plays a pivotal role in a myriad of cellular signaling pathways. Misguided protein-protein interactions (PPIs) have been linked to neurodegenerative diseases such as Alzheimer’s diseases and Parkinson’s disease, and the inhibition of protein dimerization/oligomerization has been proposed as a potential therapeutic treatment for cancer [ 48 , 49 , 50 ]. The biological significance of PPIs is further reflected by the increasing number of peptide-based drugs made available over the years, prompting the need to understand the mechanism governing the binding of peptide ligands to proteins.…”

Section: Computational Methods For the Conformational Study Of Promentioning

confidence: 99%

Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems

Lazim

Suh

Choi

2020

IJMS

109

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Molecular dynamics (MD) simulation is a rigorous theoretical tool that when used efficiently could provide reliable answers to questions pertaining to the structure-function relationship of proteins. Data collated from protein dynamics can be translated into useful statistics that can be exploited to sieve thermodynamics and kinetics crucial for the elucidation of mechanisms responsible for the modulation of biological processes such as protein-ligand binding and protein-protein association. Continuous modernization of simulation tools enables accurate prediction and characterization of the aforementioned mechanisms and these qualities are highly beneficial for the expedition of drug development when effectively applied to structure-based drug design (SBDD). In this review, current all-atom MD simulation methods, with focus on enhanced sampling techniques, utilized to examine protein structure, dynamics, and functions are discussed. This review will pivot around computer calculations of protein-ligand and protein-protein systems with applications to SBDD. In addition, we will also be highlighting limitations faced by current simulation tools as well as the improvements that have been made to ameliorate their efficiency.

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Protein-protein interactions underlying the behavioral and psychological symptoms of dementia (BPSD) and Alzheimer’s disease

Cited by 15 publications

References 164 publications

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

<p>Current Challenges and Opportunities in Designing Protein–Protein Interaction Targeted Drugs</p>

Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems

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