Article
Clinical Neurology
Amelia Strom, Leonardo Iaccarino, Lauren Edwards, Orit H. Lesman-Segev, David N. Soleimani-Meigooni, Julie Pham, Suzanne L. Baker, Susan M. Landau, William J. Jagust, Bruce L. Miller, Howard J. Rosen, Maria Luisa Gorno-Tempini, Gil D. Rabinovici, Renaud La Joie
Summary: Posterior cortical hypometabolism measured with F-18-fluorodeoxyglucose (FDG)-PET is a marker of neurodegeneration in Alzheimer's disease, and it is mainly associated with structural neurodegeneration and tau pathology, rather than amyloid pathology.
Review
Biochemistry & Molecular Biology
Leszek Szablewski
Summary: Alzheimer's disease is the most common cause of dementia in elderly people, with aging being a main risk factor. Impairment of brain energy and glucose hypometabolism are hallmarks of the disease. There are several hypotheses on the role of glucose hypometabolism in AD, but further investigations are needed on this subject.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Haidy Abbas, Nesrine S. El Sayed, Nancy Abdel Hamid Abou Youssef, Passent M. E. Gaafar, Mohamed R. Mousa, Ahmed M. Fayez, Manal A. Elsheikh
Summary: In this study, a non-invasive intranasal delivery system using novel chitosan decorated nanoparticles was developed and evaluated for the treatment of cognitive dysfunction in Alzheimer's disease. The results showed that the chitosan decorated nanoparticles improved cognitive function in an animal model of Alzheimer's disease, indicating their potential as a safe and effective therapeutic approach.
Review
Biochemistry & Molecular Biology
Chang Youn Lee, In Soo Ryu, Jin-Hyeob Ryu, Hyun-Jeong Cho
Summary: Alzheimer's disease is a progressive neurodegenerative disorder, with miRNAs playing a crucial role in its pathological processes. Limitations of current pharmaceutical therapies have led to research on miRNA-based next-generation therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Ji Yeon Oh, Eui Jin An, Young Lee, Seung Min Kim, Miju Cheon, Jun Yup Kim
Summary: The study investigates the brain glucose metabolism associated with the oral and pharyngeal phases of dysphagia in Parkinson's disease. The results show that oral phase dysphagia is associated with hypermetabolism in the right inferior temporal gyrus, bilateral cerebellum, superior frontal gyrus, and anterior cingulate cortices, as well as hypometabolism in the bilateral orbital and triangular parts of the inferior to middle frontal gyrus. Pharyngeal phase dysphagia is related to hypermetabolism of posterior aspects of the bilateral parietal lobes, cerebellum, and hypometabolism of the mediodorsal aspects of anterior cingulate and middle to superior frontal gyri.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Cell Biology
Snehal Raut, Aditya Bhalerao, Michael Powers, Minelly Gonzalez, Salvatore Mancuso, Luca Cucullo
Summary: The brain relies on glucose as its main source of energy, which is transported across the blood-brain barrier by glucose transporters. Glucose is then metabolized into ATP to support cellular functions. Medical conditions like Alzheimer's disease and Parkinson's disease can impair brain metabolism, leading to neurological symptoms.
Article
Medicine, Research & Experimental
Benita Wiatrak, Paulina Jawien, Agnieszka Matuszewska, Adam Szelag, Adriana Kubis-Kubiak
Summary: This study aimed to investigate the impact of amyloid fragments on oxidative stress and found that amyloid fragments have antioxidant properties, protecting neurons from neuroinflammation-induced damage. Among the tested fragments, the 1-40 fragment showed a stronger antioxidant effect.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Kamila Kopec, Stanislaw Szleszkowski, Dariusz Koziorowski, Stanislaw Szlufik
Summary: Neurodegenerative diseases are complex and not fully understood. Insufficiency of the glymphatic system and mitochondrial disorders play roles in the development of pathology. These factors interact and drive each other, potentially leading to protein accumulation, impaired glymphatic clearance, and sleep disorders. Clarifying the connection between the glymphatic system and mitochondria in relation to neurodegeneration could lead to new multidirectional therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Indira Y. Rao, Leah R. Hanson, Julia C. Johnson, Michael H. Rosenbloom, William H. Frey
Summary: This study aims to examine the relationship between glucose hypometabolism (GHM) and brain iron accumulation (BIA) in different regions of the brain in late-onset Alzheimer's disease (AD) or Parkinson's disease (PD) patients. The findings suggest that GHM and BIA exist independently in various brain regions in both AD and PD, indicating that they may not always be necessary or sufficient to cause each other.
Review
Clinical Neurology
Sugumar Mani, Murugan Sevanan, Alagudurai Krishnamoorthy, Sathiya Sekar
Summary: Parkinson's disease is a chronic and progressive neurodegenerative disorder affecting approximately 1% of the global population. The etiology of PD is likely multifactorial, involving protein misfolding, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Mitochondrial dysfunction plays a key role in dopaminergic neuronal loss in PD, potentially leading to neuroinflammation and vice versa. Mitochondrial proteins are a promising target for PD development, but limited dopaminergic neurons hinder detailed investigation of mitochondrial dysfunction in PD.
NEUROLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, Isabella Russo
Summary: The accumulation of amyloid-beta in Alzheimer's disease (AD) brains causes reactive astrogliosis and neuroinflammatory response. This study investigates the role of leucine-rich repeat kinase 2 (LRRK2) in regulating astrocytic activation in response to amyloid-beta(1-42) (A beta(1-42)). The results demonstrate that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of A beta(1-42) deposits, suggesting a potential contribution of PD-linked LRRK2 to AD-related neuroinflammation and pathogenesis.
Review
Cell Biology
Chia-Wei Huang, Nicholas C. Rust, Hsueh-Fu Wu, Gerald W. Hart
Summary: Alzheimer's disease, affecting over 6.5 million people in the US in 2021, is a neurodegenerative disease with an unclear etiology, especially sporadic cases. Reduced glucose uptake and hypometabolism have been implicated in the pathogenesis of Alzheimer's disease, with altered mitochondrial functions as a contributing factor. The lack of appropriate models to study early molecular changes in Alzheimer's disease progression is a major challenge in research, necessitating the development of a human neuronal model that better represents sporadic Alzheimer's disease as a metabolic disorder.
NEURAL REGENERATION RESEARCH
(2023)
Article
Immunology
Kelly Ceyzeriat, Thomas Zilli, Philippe Millet, Nikolaos Koutsouvelis, Giovanna Dipasquale, Christine Fossey, Thomas Cailly, Frederic Fabis, Giovanni B. B. Frisoni, Valentina Garibotto, Benjamin B. B. Tournier
Summary: Low-dose brain radiation therapy has been shown to reduce neuroinflammation, lower amyloid levels, and improve cognitive performances in animal models of Alzheimer's disease.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Immunology
Deepali Singh
Summary: Neuroinflammation is caused by the misfiring of immune cells in the central nervous system and can have both positive and negative effects on neurodevelopment and post-injury tissue. Chronic or uncontrolled inflammatory responses may lead to neurodegenerative diseases, while abnormal activation of glial cells can mediate neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Pharmacology & Pharmacy
Christian Holscher
Summary: Type 2 diabetes and insulin desensitization have been linked to neurodegenerative disorders like Alzheimer's and Parkinson's diseases. GLP-1 and GIP hormones have shown neuroprotective effects in trials, suggesting potential disease-modifying care for patients.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Amy Keerie, Heledd Brown-Wright, Isaac Kirkland, Andrew Grierson, James J. P. Alix, Christian Holscher, Richard J. Mead
Summary: This study investigated the effects of the GLP-1 receptor agonist liraglutide in transgenic mouse models of ALS, but found no significant impact on disease progression or motor neuron counts compared to vehicle-treated mice. The results do not support clinical evaluation of liraglutide as a potential candidate for the treatment of ALS.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Guang-Zhao Yang, Qi-Chao Gao, Wei-Ran Li, Hong-Yan Cai, Hui-Min Zhao, Jian-Ji Wang, Xin-Rui Zhao, Jia-Xin Wang, Mei-Na Wu, Jun Zhang, Christian Holscher, Jin-Shun Qi, Zhao-Jun Wang
Summary: (D-Ser2) Oxyntomodulin improves cognitive function in Alzheimer's disease transgenic mice by restoring hippocampal synaptic function and theta rhythm.
NEURAL REGENERATION RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Xiaoyan Yang, Peng Feng, Rong Ji, Yiqing Ren, Wenshi Wei, Christian Holscher
Summary: The review summarizes preclinical and clinical studies testing GLP-1R agonists and dual GLP-1/GIPR agonists in PD and discusses possible mechanisms of action.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Neurosciences
Zijuan Zhang, Hai Li, Yunfang Su, Jinlian Ma, Ye Yuan, Ziyang Yu, Ming Shi, Simai Shao, Zhenqiang Zhang, Christian Holscher
Summary: Research demonstrates that the CCK analogue has neuroprotective effects and improves locomotor function in an acute PD mouse model. It acts by restoring dopaminergic neuron count and synapse number, reducing neuroinflammation and autophagy impairment, and protecting against mitochondrial and ER damage.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Clinical Neurology
Xiaoyan Yang, Qiang Qiang, Nan Li, Peng Feng, Wenshi Wei, Christian Hoelscher
Summary: The global burden of ischemic stroke, a major public and social health concern, is on the rise. Hyperglycemia increases the risk of stroke, particularly in patients with diabetes. Treatment for ischemic stroke focuses on restoring cerebral blood flow and improving neurological impairment. GLP-1 RAs are considered to have neuroprotective effects in ischemic stroke.
FRONTIERS IN NEUROLOGY
(2022)
Article
Pharmacology & Pharmacy
Yunfang Su, Ningning Liu, Zijuan Zhang, Hao Li, Jinlian Ma, Ye Yuan, Ming Shi, Jihong Liu, Zhenrong Zhao, Zhenqiang Zhang, Christian Holscher
Summary: Parkinson's disease (PD) is a common neurodegenerative disease, with colonic pathology appearing before brain pathology in PD patients. CCK and GLP-1 analogues show potential in improving colonic pathology, reducing inflammation, inhibiting dopaminergic neuron damage, and decreasing the accumulation of alpha-synuclein in the colons of PD mouse models.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Neurosciences
Christian Holscher
Summary: GLP-1 and GIP receptor agonists have shown protective effects on synapses and synaptic transmission in the treatment of AD and PD. Through animal models and clinical trials, these receptor agonists have demonstrated good effects in preventing cognitive decline, synaptic loss, and neuron death. By enhancing the ability to cross the blood-brain barrier, dual-GLP-1/GIP receptor agonists have shown superior protective properties in the prevention and treatment of AD and PD.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Hongyan Cai, Jing Qiao, Siru Chen, Junting Yang, Christian Holscher, Zhaojun Wang, Jinshun Qi, Meina Wu
Summary: This study reveals that MCU knockdown in hippocampal neurons can improve the memory performance of APP/PS1/tau mice. The results suggest that MCU knockdown can improve the synapse structure and function, alleviate inflammation, and restore mitophagy, indicating its potential as a therapeutic approach for AD.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Behavioral Sciences
Niklas Reich, Christian Holscher
Summary: This review examines the role of acylated ghrelin in the regulation of memory and fear behavior, as well as its impact on specific brain areas and neurotransmitter systems. It also discusses the neurogenesis and signaling pathways associated with acylated ghrelin in the hippocampus, and its involvement in conditioned taste aversion, novelty learning, and memory formation.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Clinical Neurology
Lingyu Zhang, Chun Li, Zijuan Zhang, Zhenqiang Zhang, Qian-Qian Jin, Lin Li, Christian Holscher
Summary: The study found that DA5-CH was more effective than semaglutide in a PD model, reducing rotational behavior, alleviating dopamine depletion and inflammation response, protecting dopaminergic neurons, and reducing levels of α-synuclein.
PARKINSONS DISEASE
(2022)
Article
Neurosciences
Zijuan Zhang, Ziyang Yu, Ye Yuan, Jing Yang, Shijie Wang, He Ma, Li Hao, Jinlian Ma, Zhonghua Li, Zhenqiang Zhang, Christian Hölscher
Summary: Synaptic impairment and loss are important in Alzheimer's disease (AD), and can cause cognitive dysfunction and memory loss. In this study, a novel CCK analogue was found to improve synaptic plasticity, spatial learning, and memory in an AD mouse model. This effect was achieved through the activation of the PI3K/Akt and PKA/CREB-BDNF/TrkB signaling pathways, leading to protection of synapses and cognition.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Genetics & Heredity
Hong-Yan Cai, Si-Ru Chen, Yu Wang, Juan-Juan Jiao, Jun Qiao, Christian Holscher, Zhao-Jun Wang, Sheng-Xiao Zhang, Mei-Na Wu
Summary: Alzheimer's disease (AD) is a progressive neurodegenerative disease that worsens with age. Dysregulation of long non-coding RNAs (lncRNAs) and the associated competing endogenous RNA (ceRNA) network may be linked to the occurrence and development of AD. RNA sequencing identified 358 differentially expressed genes (DEGs), including 302 differentially expressed mRNAs (DEmRNAs) and 56 differential expressed lncRNAs (DElncRNAs). The constructed ceRNA network includes 4 lncRNAs, 4 microRNAs, and 2 mRNAs. Functional enrichment analysis revealed the involvement of DEmRNAs in AD-related biological functions. Co-expressed DEmRNAs in humans and mice were validated using real-time quantitative polymerase chain reaction (qRT-PCR). The findings provide insights into AD-related pathological mechanisms and can contribute to improving AD diagnosis and treatment.
Article
Neurosciences
Theodora Panagaki, Elisa B. Randi, Csaba Szabo, Christian Holscher
Summary: The study confirms the protective effects of incretin signaling in managing neuronal degeneration in Parkinson's disease, and further explains the observed effects of incretin-based therapies in PD patients. The dual incretin analog shows superior anti-apoptotic effects compared to the glucagon-like peptide-1 analog.
JOURNAL OF PARKINSONS DISEASE
(2023)