Article
Biochemistry & Molecular Biology
Yue Huang, Wenbin Zhang, Xiaorou Guo, Ying Zhang, Junfeng Wu, Hengbing Zu
Summary: In the past 20 years, studies on cell cultures have indicated contradictory findings regarding the relationship between cholesterol levels and amyloid-beta (A beta) production in Alzheimer's disease. This study introduces new cell models induced by DHCR24, which differ from previous models with overexpressed amyloid precursor protein (APP). The results show that cellular cholesterol deficiency increases A beta production, and the disruption of cellular cholesterol homeostasis by APP overexpression might contribute to this effect.
JOURNAL OF LIPID RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Victoria Campos-Pena, Pavel Pichardo-Rojas, Talia Sanchez-Barbosa, Emma Ortiz-Islas, Citlali Ekaterina Rodriguez-Perez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios
Summary: The presence of insoluble aggregates of amyloid beta (A beta) in the brain is a hallmark of Alzheimer's disease, and it has been shown to contribute to extensive neuronal loss. The distribution and content of cholesterol in the membrane play an important role in the production and accumulation of A beta peptides, leading to dysfunction and neuronal death. The monomeric forms of A beta peptides can trigger changes in Tau phosphorylation and cognitive function through their internalization by specific receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nikhil Agrawal, Adam A. Skelton, Emilio Parisini
Summary: Alzheimer's disease, characterized by the misfolding and aggregation of amyloid-beta (A beta) peptides, remains poorly understood in terms of its molecular mechanism of interaction with cell membranes. In this study, simulations were conducted to investigate the interaction between A beta 1-40 fibrils and different bilayers composed of DPPC and cholesterol. The results show the involvement of hydrophobic amino acid clusters, lysine residues, and C-terminal hydrophobic residues in the binding process. Furthermore, the data suggest that the binding affinity of A beta 1-40 fibrils to the membrane increases with the presence of cholesterol. These findings provide insights into potential target regions for the development of inhibitors against A beta oligomer/fibril-membrane interaction.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Neurosciences
Linda Hanbouch, Beatrice Schaack, Amal Kasri, Gaelle Fontaine, Eleni Gkanatsiou, Gunnar Brinkmalm, Elena Camporesi, Erik Portelius, Kaj Blennow, Gilles Mourier, Nicolas Gilles, Mark J. Millan, Catherine Marquer, Henrik Zetterberg, Lydie Boussicault, Marie-Claude Potier
Summary: Excess brain cholesterol is strongly associated with Alzheimer's disease. This study found that the presence of a cholesterol-binding site in the amyloid precursor protein (APP) regulates its processing. Mutations in this site affected the secretion of amyloid-beta peptides and produced shorter toxic peptides. Cholesterol levels also influenced the production of these peptides, with higher cholesterol resulting in increased production.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shirin Azizidoost, Hossein Babaahmadi-Rezaei, Zahra Nazeri, Maryam Cheraghzadeh, Alireza Kheirollah
Summary: A beta significantly increased the levels of cholesterol synthesis enzyme and ABC transporter A1 protein in both astrocytes and neurons, as well as cellular cholesterol content, without increasing cholesterol efflux. Interestingly, when A beta-pretreated neurons were exposed to astrocyte media, the levels of cholesterol synthesis enzyme HMGCR were restored, indicating a potential regulatory role of astrocytes in brain cholesterol metabolism affected by A beta.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Biochemistry & Molecular Biology
Urszula Orzel, Jakub Jakowiecki, Krzysztof Mlynarczyk, Slawomir Filipek
Summary: The study showed that at high cholesterol levels, Aβ(45) was more flexible in the binding site of presenilin than Aβ(43), but the active site of presenilin at the C-terminal part of Aβ(45) was more compact, which could promote processing of this substrate. Cholesterol binding sites at low and high concentrations were also mapped, independent of typical cholesterol binding motifs.
Article
Genetics & Heredity
Nathalie I. V. Nilsson, Cynthia Picard, Anne Labonte, Theresa Koebe, Pierre-Francois Meyer, Sylvia Villeneuve, Daniel Auld, Judes Poirier
Summary: This study suggests that genetics underlying peripheral blood total cholesterol levels could influence the risk of developing Alzheimer's disease, but no association was found between the genetic score and AD pathology or cognitive impairment.
Review
Biochemistry & Molecular Biology
Steve Pedrini, Pratishtha Chatterjee, Eugene Hone, Ralph N. Martins
Summary: HDL plays a crucial role in removing excess cholesterol and has additional benefits such as anti-oxidant and anti-inflammatory properties. Proteins associated with HDL, known as 'protein cargo', have been extensively analyzed through mass spectrometry to understand their role in health and disease.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins
Summary: The composition and functionality of HDL are altered in Alzheimer's Disease patients, which may impact regional brain volumetric data.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Cell Biology
Qi Wu, Leonardo Cortez, Razieh Kamali-Jamil, Valerie Sim, Holger Wille, Satyabrata Kar
Summary: The study found that exosomes derived from cholesterol-accumulated astrocytes contain higher levels of A beta peptide, indicating their importance in AD pathology. In addition, exosomes may also lead to neurodegeneration, which can be attenuated by decreasing A beta production or using anti-A beta antibody.
DISEASE MODELS & MECHANISMS
(2021)
Review
Biochemistry & Molecular Biology
Oscar M. Munoz M. Herrera, Angela M. M. Zivkovic
Summary: Cholesterol plays a crucial role in brain function and structure, and its dysregulation has been associated with neurodegenerative diseases such as Alzheimer's disease. While the regulation and dysregulation of cholesterol metabolism and transport in neurons and astrocytes are well-studied, less is known about how microglia, the immune cells of the brain, handle cholesterol and how this affects their functions. This review discusses the role of cholesterol in regulating microglia phenotype and function, the effects of statins on microglia, and highlights areas for future research to develop novel therapies for the prevention and treatment of Alzheimer's disease.
Article
Clinical Neurology
Nanet Willumsen, Teresa Poole, Jennifer M. Nicholas, Nick C. Fox, Natalie S. Ryan, Tammaryn Lashley
Summary: This study found significant heterogeneity in A beta pathology among familial Alzheimer's disease cases, with different mutations potentially leading to varying patterns of A beta deposition. Carriage of the APOE4 allele may be associated with increased disease duration but not age at onset.
Article
Biochemistry & Molecular Biology
Oscar Munoz M. Herrera, Brian V. V. Hong, Ulises Ruiz Mendiola, Izumi Maezawa, Lee-Way Jin, Carlito B. Lebrilla, Danielle J. Harvey, Angela M. Zivkovic
Summary: Research has shown that specific genes in microglia are highly associated with Alzheimer's disease (AD) and microglia play a critical role in the development of AD. Therefore, microglia are an important target for novel AD treatment approaches. A study used a multi-stimulant approach to examine the human microglia cell 3 (HMC3) cell line's ability to replicate dysfunctional microglia characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Geriatrics & Gerontology
Frank R. Sharp, Charles S. DeCarli, Lee-Way Jin, Xinhua Zhan
Summary: White matter injury, cholesterol dysmetabolism, and Abeta dysmetabolism interact to contribute to the development and worsening of Alzheimer's disease pathology. These factors, combined with genetic and age-related risk factors, lead to increased levels of Abeta and amyloid plaques. Furthermore, these processes also contribute to myelin damage.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Cell Biology
Shwetha Nanjundaiah, Hariharakrishnan Chidambaram, Madhura Chandrashekar, Subashchandrabose Chinnathambi
Summary: Cholesterol, a crucial component of the cell membrane, plays a significant role in the brain by influencing synaptic transmission, neuronal signaling, and neurodegenerative diseases. Dysregulation of cholesterol trafficking is linked to increased production of hyperphosphorylated Tau and Amyloid-beta protein, leading to Alzheimer's disease. Understanding the regulation of cholesterol metabolism and Tau phosphorylation is essential for managing the pathogenesis of Alzheimer's disease.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell & Tissue Engineering
Henri J. Huttunen, Mart Saarma
CELL TRANSPLANTATION
(2019)
Review
Biochemistry & Molecular Biology
Cecilia A. Brunello, Maria Merezhko, Riikka-Liisa Uronen, Henri J. Huttunen
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Maria Merezhko, Emmi Pakarinen, Riikka-Liisa Uronen, Henri J. Huttunen
BIOSCIENCE REPORTS
(2020)
Article
Medicine, Research & Experimental
Tommi P. Kilpelainen, Laura Hellinen, Johannes Vrijdag, Xu Yan, Reinis Svarcbahs, Kati-Sisko Vellonen, Anne-Marie Lambeir, Henri Huttunen, Arto Urtti, Erik A. A. Wallen, Timo T. Myohanen
BIOMEDICINE & PHARMACOTHERAPY
(2020)
Review
Neurosciences
Roger A. Barker, Anders Bjorklund, Don M. Gash, Alan Whone, Amber Van Laar, Jeffrey H. Kordower, Krystof Bankiewicz, Karl Kieburtz, Mart Saarma, Sigrid Booms, Henri J. Huttunen, Adrian P. Kells, Massimo S. Fiandaca, A. Jon Stoessl, David Eidelberg, Howard Federoff, Merja H. Voutilainen, David T. Dexter, Jamie Eberling, Patrik Brundin, Lyndsey Isaacs, Leah Mursaleen, Eros Bresolin, Camille Carroll, Alasdair Coles, Brian Fiske, Helen Matthews, Codrin Lungu, Richard K. Wyse, Simon Stott, Anthony E. Lang
JOURNAL OF PARKINSONS DISEASE
(2020)
Article
Multidisciplinary Sciences
Anastasia Ludwig, Sebnem Kesaf, Joonas J. Heikkinen, Tatiana Sukhanova, Shokoufeh Khakipoor, Florence Molinari, Christophe Pellegrino, Sung Kim, Jeon G. Han, Henri J. Huttunen, Sari E. Lauri, Sami Franssila, Ville Jokinen, Claudio Rivera
SCIENTIFIC REPORTS
(2020)
Review
Neurosciences
Maria Merezhko, Riikka-Liisa Uronen, Henri J. Huttunen
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2020)
Article
Biotechnology & Applied Microbiology
Katrina Albert, Diana P. Raymundo, Anne Panhelainen, Ave Eesmaa, Liana Shvachiy, Gabriela R. Araujo, Piotr Chmielarz, Xu Yan, Aastha Singh, Yraima Cordeiro, Fernando L. Palhano, Debora Foguel, Kelvin C. Luk, Andrii Domanskyi, Merja H. Voutilainen, Henri J. Huttunen, Tiago F. Outeiro, Mart Saarma, Marcius S. Almeida, Mikko Airavaara
Summary: CDNF interacts with alpha-synuclein to reduce its aggregation and internalization, while inducing the formation of insoluble phosphorylated alpha-synuclein. However, the beneficial effects of CDNF on rodent behavior do not seem to be related to the number of phosphorylated alpha-synuclein inclusions formed. Further study is needed to understand its effects on aggregation mechanism in vivo.
Article
Multidisciplinary Sciences
Hanna Julku, Santeri Rouhinen, Henri J. Huttunen, Laura Lindberg, Johanna Liinamaa, Ville Saarela, Elina Karvonen, Sigrid Booms, Jyrki P. Makela, Hannu Uusitalo, Eero Castren, J. Matias Palva, Satu Palva
Summary: In patients with anisometric amblyopia, oscillation amplitudes and evoked responses are reduced when stimuli are presented to the amblyopic eye in higher-order visual areas, parietal and prefrontal cortices. Importantly, the reduction of oscillation amplitudes is correlated with decreased visual acuity in amblyopia.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Marianna Hellen, Arnab Bhattacharjee, Riikka-Liisa Uronen, Henri J. Huttunen
Summary: The study reveals that tau protein secretes through membrane interaction via forming disulphide bridges, allowing it to penetrate protein-free membranes independently of cellular processes. The modeling of the microtubule-binding repeat domains (MTBDs) suggests that certain regions of tau could form transient amphipathic helices for membrane interaction.
BIOSCIENCE REPORTS
(2021)
Article
Clinical Neurology
Henri J. J. Huttunen, Sigrid Booms, Magnus Sjogren, Vera Kerstens, Jarkko Johansson, Rebecka Holmnas, Jani Koskinen, Natalia Kulesskaya, Patrik Fazio, Max Woolley, Alan Brady, Julia Williams, David Johnson, Narges Dailami, William Gray, Reeta Levo, Mart Saarma, Christer Halldin, Johan Marjamaa, Julio Resendiz-Nieves, Irena Grubor, Goran Lind, Johanna Eerola-Rautio, Tuomas Mertsalmi, Mattias Andreasson, Gesine Paul, Juha Rinne, Riku Kivisaari, Hjalmar Bjartmarz, Per Almqvist, Andrea Varrone, Filip Scheperjans, Hakan Widner, Per Svenningsson
Summary: This study aimed to assess the safety and tolerability of CDNF and the drug delivery system (DDS) in patients with PD. The results showed that the CDNF treatment was safe and well tolerated, with possible signs of biological response. This study is of great importance for the development of treatment methods for PD.
MOVEMENT DISORDERS
(2023)
Article
Cell Biology
Kuan-Yin Tseng, Vassilis Stratoulias, Wei-Fen Hu, Jui-Sheng Wu, Vicki Wang, Yuan-Hao Chen, Anna Seelbach, Henri J. Huttunen, Natalia Kulesskaya, Cheng-Yoong Pang, Jian-Liang Chou, Maria Lindahl, Mart Saarma, Li-Chuan Huang, Mikko Airavaara, Hock-Kean Liew
Summary: During intracerebral hemorrhage (ICH), hematoma formation leads to local mechanical injury, and the release of hemoglobin and heme induces inflammation and secondary brain injury. Modulating immune cells to promote hematoma resorption and reduce brain edema has potential as a therapeutic strategy for functional recovery after ICH.
CELL DEATH & DISEASE
(2023)
Review
Cell Biology
Xu Yan, Riikka-Liisa Uronen, Henri J. Huttunen
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2020)
Meeting Abstract
Clinical Neurology
H. Huttunen, S. Booms, J. Koskinen, M. Saarma
MOVEMENT DISORDERS
(2018)
Meeting Abstract
Clinical Neurology
S. Sulkava, P. Muggalla, R. Sulkava, H. M. Ollila, T. Peuralinna, L. Myllykangas, S. Helisalmi, H. Soininen, T. Polvikoski, M. Hiltunen, P. J. Tienari, H. J. Huttunen, T. Paunio
JOURNAL OF SLEEP RESEARCH
(2018)