Article
Clinical Neurology
Constance Delaby, Teresa Estelles, Nuole Zhu, Javier Arranz, Isabel Barroeta, Maria Carmona-Iragui, Ignacio Illan-Gala, Miguel Angel Santos-Santos, Miren Altuna, Isabel Sala, M. Belen Sanchez-Saudinos, Laura Videla, Silvia Valldeneu, Andrea Subirana, Mireia Tondo, Francisco Blanco-Vaca, Sylvain Lehmann, Olivia Belbin, Rafael Blesa, Juan Fortea, Alberto Lleo, Daniel Alcolea
Summary: This study compared the differences in CSF A beta 1-42 and A beta 1-42/A beta 1-40 ratio in different neurodegenerative disorders and found that the A beta 1-42/A beta 1-40 ratio was strongly correlated with tTau and pTau181. Patients with a low A beta 1-42/A beta 1-40 ratio showed higher levels of tTau and pTau181 and worse cognitive and functional prognosis, regardless of A beta 1-42 positivity.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Nutrition & Dietetics
Lifang Zhang, Jessica Cao, Haiqiang Yang, Phillip Pham, Umer Khan, Breanna Brown, Yanhong Wang, Tarek Zieneldien, Chuanhai Cao
Summary: Coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of A beta-related Alzheimer's disease (AD). All coffees tested have beneficial health effects for AD through lowering A beta 1-40 and A beta 1-42 production, with Dunkin' Donuts (R) medium roast coffee demonstrating the most consistent and optimal cell survival rates and A beta concentration, while Starbucks (R) coffee exhibited the highest cell toxicity rates among the tested coffees.
FRONTIERS IN NUTRITION
(2022)
Article
Chemistry, Multidisciplinary
Saja Mohammed Abdulkareem, M. R. Housaindokht, M. R. Bozorgmehr
Summary: This paper examines the interaction between amyloid-beta and two different surfactants, showing their effects on the aggregation of the protein. The calculations suggest potential interactions between peptide residues and surfactants.
JOURNAL OF THE IRANIAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Xinyi Su, Zhiqun Tang, Zhiyue Lu, Yuqiu Liu, Wanzhi He, Jiapei Jiang, Yifan Zhang, Hongkun Wu
Summary: The study indicates that Treponema denticola can enter the brain and directly affect nerve cells, resulting in the accumulation of A beta. Inhibitors such as KMI1303 and DAPT can suppress the effect of T. denticola on A beta.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Meilin She, Suhang Shang, Ningwei Hu, Chen Chen, Liangjun Dang, Ling Gao, Shan Wei, Kang Huo, Jingyi Wang, Jin Wang, Qiumin Qu
Summary: The study found that elevated blood pressure levels were positively correlated with increased plasma A beta(1-40) levels in middle-aged and elderly ApoE epsilon 4 non-carriers.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Victoria Monge-Garcia, Lourdes Llorca-Tolon, Ruth Gasparini-Berenguer, Jose A. Monge-Argiles
Summary: This study aimed to evaluate the diagnostic gain of calculating the A beta(1-42)/A beta(1-40) ratio in identifying MCI patients with AD, compared to using only A beta(1-42). The results showed that using the A beta(1-42)/A beta(1-40) ratio significantly increased the accuracy of diagnosing amyloidosis in cerebrospinal fluid compared to using only A beta(1-42) levels.
REVISTA DE NEUROLOGIA
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Hariom Soni, Manoj Kumar Goyal, Phulen Sarma, Harmandeep Singh, Manish Modi, Anchal Sharma, Manju Mohanty, Venugopalan Y. Vishnu, Ashok Kumar, Bhagwant Rai Mittal, Bikash Medhi
Summary: The study indicated that plasma A beta(1-42) level as a diagnostic biomarker of AD showed good specificity but low sensitivity in the Indian population. There was a significant correlation between A beta(1-40)/A beta(1-42) ratio and 18F-FDG PET Z score in different brain regions.
INDIAN JOURNAL OF NUCLEAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: This article discusses the concept of productive signaling, including its definition, measurement, and determining factors. It highlights the importance of understanding signal propagation in diseases like cancer and neurodevelopmental disorders. The authors propose a framework for investigating signal transduction by defining cellular processes, conducting experimental measurements, and utilizing computational AI algorithms.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Biophysics
Yonglan Liu, Hyunbum Jang, Mingzhen Zhang, Chung-Jung Tsai, Ryan Maloney, Ruth Nussinov
Summary: This study provides insights into the molecular mechanism of BCR-ABL recruitment of GRB2, revealing the determinants of specificity in the recognition between SH2(GRB2) and phosphorylated BCR. The findings contribute to the prediction of BCR-binding scaffolds and the design of therapeutic peptides.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ryan C. Maloney, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Interactions between MEK1, B-Raf, and KSR1 are crucial for Ras/Raf/MEK/ERK signaling. Molecular dynamics simulations reveal that the proline-rich loop of MEK1 is essential for the phosphorylation of MEK1 activation loop. In the inactive B-Raf/MEK1 complex, the collapsed A-loop of B-Raf interacts with the P-rich loop and A-loop of MEK1, preventing phosphorylation. In the active B-Raf/MEK1 complex, the P-rich loop moves with the extended A-loop of B-Raf, leading to increased A-loop fluctuation and phosphorylation. KSR1/MEK1 complex has fewer interactions between KSR1 alpha G-helix and MEK1 A-loop, resulting in a more flexible A-loop.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hansaim Lim, Fatma Cankara, Chung -Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This review discusses recent advancements in computational methods for predicting microbial effects on human cells, with a focus on protein-protein interactions. Traditional methods, as well as more recent deep learning methods, are categorized and potential solutions to challenges in structure-based approaches are discussed. The review provides a brief guide to the current status and future directions in the field.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Chung -Jung Tsai, Hyunbum Jang
Summary: This article discusses the principles and applications of allosteric activating mutations and drugs, using examples from the Ras signaling network. Specifically, it focuses on Abl kinase mutations that shift the conformation towards an active state, leading to competition between high affinity ATP and drug binding. Recent pharmacological innovation includes allosteric inhibitors and allosteric heterobifunctional degraders that can destroy targets. The design of chemical linkers in bifunctional degraders allows precise coordination between the target protein and the E3 ubiquitin ligase, enabling innovative drug discovery.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Multidisciplinary Sciences
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: Immunity plays a crucial role in both neurodevelopmental disorders and cancer, as the immune and nervous systems coevolve during embryonic development. Dysregulated signaling caused by germline or embryonic mutations can lead to changes in chromatin organization and gene accessibility, affecting the expression of essential genes in neurodevelopment. Similarly, dysregulated signaling resulting from somatic mutations contributes to cancer development. Both conditions involve small GTPases and their pathways, as well as dysregulation of TLRs, IL-1, GIT1, and FGFR signaling pathways. However, key differentiating factors are the timing and level of perturbation in specific cell types, indicating chromatin reorganization.
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.
Letter
Oncology
Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
CANCER COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Ruth Nussinov, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang
Summary: Drug discovery is a highly challenging and significant interdisciplinary aim. The success of AlphaFold, an AI-powered technology, has raised hopes for drug discovery, but its limitations need to be considered. Improving AlphaFold's performance in active state models can enhance the success rate of rational drug design.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Biophysics
Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Mingzhen Zhang, Yonglan Liu, Chung-Jung Tsai, Hyunbum Jang, Nurcan Tuncbag
Summary: Neurodevelopmental disorders (NDDs) and cancer have similarities in terms of proteins, pathways, and mutations, but have different clinical symptoms. However, individuals with NDDs have a higher likelihood of developing cancer later on. This review explores how shared features can result in different medical conditions and why having an NDD first can increase the chances of malignancy.
BIOPHYSICAL REVIEWS
(2023)
Article
Genetics & Heredity
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag
Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The propensities of protein conformations can predict cell function and suggest drug efficiency.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The sequence-structure-function paradigm in molecular biology has been updated to include the concept of conformational ensembles, recognizing that proteins are dynamic and constantly transitioning between different conformational states. The number and stability of these states are crucial for protein function. Understanding conformational propensities is essential for studying diverse systems and can provide insights into the dynamics of protein ensembles in cells.
RSC CHEMICAL BIOLOGY
(2023)
Article
Genetics & Heredity
Dana Mary Varghese, Ruth Nussinov, Shandar Ahmad
Summary: Moonlighting proteins are capable of performing multiple autonomous functions. In this study, human moonlighting DNA-binding proteins (mDBPs) were investigated and found to be distinguishable from other proteins with the same DNA-binding function. A machine learning model was developed to predict mDBPs from other DBPs with high accuracy.
NAR GENOMICS AND BIOINFORMATICS
(2022)