Article
Biochemistry & Molecular Biology
Ye Wang, Joakim Bergstrom, Martin Ingelsson, Gunilla T. T. Westermark
Summary: This study investigates the interaction between alpha-synuclein (aSyn) and islet amyloid polypeptide (IAPP) in Alzheimer's disease and type 2 diabetes. The results show intracellular co-localization of aSyn with IAPP, but aSyn is absent in the extracellular amyloid deposits. In vitro experiments demonstrate that preformed aSyn fibrils can seed IAPP fibril formation, but IAPP does not affect aSyn fibrillation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eduardo Ramirez, Susantha K. Ganegamage, Sehong Min, Henika Patel, Adedayo Ogunware, German Plascencia-Villa, Heba Alnakhala, Kazuma Shimanaka, Arati Tripathi, Kuang-Wei Wang, Xiongwei Zhu, Jean-Christophe Rochet, Min-Hao Kuo, Scott E. Counts, George Perry, Ulf Dettmer, Cristian A. Lasagna-Reeves, Jessica S. Fortin
Summary: Alzheimer's disease is the most common neurodegenerative disorder causing dementia in the elderly population. The disease is characterized by the presence of amyloid-beta and hyperphosphorylated tau protein aggregates. This article describes a drug discovery program focused on developing compounds that can reduce the aggregation of alpha-synuclein, tau isoform 2N4R, and p-tau isoform 1N4R, with the aim of slowing down the progression of Alzheimer's disease and related dementias.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Sylwia Libard, Vilmantas Giedraitis, Lena Kilander, Martin Ingelsson, Irina Alafuzoff
Summary: This study assessed neuropathological changes in a 73-year-old subject with a novel PSEN1 G206R mutation and compared them with a subject with sporadic Alzheimer's disease. The mutation carrier exhibited more extensive AD neuropathological changes and additional proteinopathies that were not observed in the sporadic AD case. The mutation carrier also displayed pronounced neuroinflammation, which has not been previously described in association with PSEN1 mutations. The study highlights the importance of thorough postmortem neuropathological and genetic assessment in understanding dementing illnesses.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Neurosciences
Guoxin Zhang, Lanxia Meng, Zhihao Wang, Qinyu Peng, Guiqin Chen, Jing Xiong, Zhentao Zhang
Summary: The study shows that IAPP interacts with tau and accelerates the formation of a more toxic strain, playing a crucial role in tau pathology in AD. Injection of IAPP-tau strain and IAPP fibrils can induce more severe tau pathology spreading and cognitive impairments.
MOLECULAR NEURODEGENERATION
(2022)
Article
Clinical Neurology
Fardin Nabizadeh, Kasra Pirahesh, Parya Valizadeh
Summary: The study found that the changes in CSF alpha-syn, t-tau, and p-tau were not significant enough to distinguish PD patients with and without RBD. However, CSF A beta 1-42 decreased in the short term and showed a significant difference after a while in PD patients with and without RBD.
JOURNAL OF NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Patients with type 2 diabetes mellitus have a significantly higher risk of developing dementia, possibly due to increased secretion of amylin. This review summarizes the mechanisms by which amylin accumulation may cause neuronal damage and discusses the importance of investigating new therapeutic targets for treating dementia.
NEURAL REGENERATION RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Kendall B. E. Moore, Ta-Jung Hung, Jessica S. Fortin
Summary: Alzheimer's disease is the most common form of dementia, characterized by neurofibrillary tangles and beta-amyloid plaques. There is currently no cure or disease-modifying therapy available. Misfolded hyperphosphorylated tau has been identified as a key factor in the pathogenesis of Alzheimer's disease and inhibiting its aggregation could be a potential therapeutic strategy.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Lucie Khemtemourian, Hebah Fatafta, Benoit Davion, Sophie Lecomte, Sabine Castano, Birgit Strodel
Summary: This study investigates the molecular details of IAPP binding to lipid membranes, revealing different membrane interaction modes and aggregation structures for different IAPP variants. Residue 18 plays a decisive role in the structure and membrane interaction of IAPP, making it a potential therapeutic target for inhibiting IAPP toxicity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Immunology
Wangyu Bi, Tong Lei, Shanglin Cai, Xiaoshuang Zhang, Yanjie Yang, Zhuangzhuang Xiao, Lei Wang, Hongwu Du
Summary: This review summarizes the role of astrocytes in Alzheimer's disease (AD) and explores the potential therapeutic strategies targeting astrocytes. Astrocytes play an important role in the pathogenesis of AD, and therapies targeting astrocytes have shown high efficacy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Noe Quittot, Mathilde Fortier, Margaryta Babych, Phuong Trang Nguyen, Mathew Sebastiao, Steve Bourgault
Summary: The study reveals that GAGs exacerbate IAPP-induced cytotoxicity and membrane perturbation, increasing the local concentration of IAPP on the cell surface and promoting lipid bilayer disturbance and cell death.
Review
Biochemistry & Molecular Biology
Anns Mahboob, Degiri Kalana Lasanga Senevirathne, Pradipta Paul, Faisal Nabi, Rizwan Hasan Khan, Ali Chaari
Summary: Type 2 diabetes is a chronic metabolic disease with a significant global disease burden. Non-genetic risk factors for T2D include obesity, diet, physical activity, lifestyle, smoking, age, ethnicity, and mental stress. The aggregation and misfolding of hIAPP have detrimental effects on beta-cell function and health. Polyphenols have shown promising potential as natural therapeutics for inhibiting hIAPP aggregation and mitigating larger pathological effects of T2D, but further studies are needed to evaluate their mechanisms of action and ideal doses.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Geriatrics & Gerontology
Petrice M. Cogswell, Heather J. Wiste, Michelle M. Mielke, Christopher G. Schwarz, Stephen D. Weigand, Val J. Lowe, Terry M. Therneau, David S. Knopman, Jonathan Graff-Radford, Prashanthi Vemuri, Matthew L. Senjem, Jeffrey L. Gunter, Alicia Algeciras-Schimnich, Ronald C. Petersen, Clifford R. Jack
Summary: This study evaluated the relationship between CSF p-tau181 and the rate of tau PET change in specific brain regions, and found associations with amyloid and CSF p-tau181 levels. The findings suggest that tau aggregation begins later in the disease process, and the entorhinal cortex may be a more sensitive marker for early tau PET changes.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Fardin Nabizadeh, Kasra Pirahesh, Elham Ramezannezhad
Summary: This study found that CSF levels of α-synuclein and Aβ1-42 were associated with the degree of dopaminergic neuron loss in the left caudate nucleus in Parkinson's disease. These findings suggest that Aβ pathology may precede dopaminergic loss in the striatal nuclei and subsequently lead to cognitive impairment in PD patients.
NEUROLOGICAL SCIENCES
(2023)
Review
Neurosciences
Urmi Sengupta, Rakez Kayed
Summary: This review summarizes the histopathological features of specific protein aggregation in several neurodegenerative diseases and discusses their overlap. It also highlights the synergistic interplay among Aβ, tau, and alpha-Syn in these diseases, suggesting a protein triumvirate.
PROGRESS IN NEUROBIOLOGY
(2022)