Review
Clinical Neurology
Isabelle K. Gorham, Robert C. Barber, Harlan P. Jones, Nicole R. Phillips
Summary: Literature suggests that the release of mtDNA in Alzheimer's disease is correlated with increased immune responses, indicating its potential as a biomarker. However, there are still unanswered questions and further research in this area is needed.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Victor Tapias, Paula Gonzalez-Andres, Laura F. Pena, Asuncion Barbero, Lucia Nunez, Carlos Villalobos
Summary: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases in the elderly, characterized by abnormal protein aggregates and loss of neurons in specific brain regions. The exact mechanisms of these diseases are unknown, but oxidative stress, mitochondrial dysfunction, and disrupted Ca2+ homeostasis play a crucial role. With an increase in life expectancy, there is a need for preventive strategies and disease-modifying therapies for AD/PD. Modulating Ca2+ homeostasis and signaling, as well as controlling mitochondrial function with heterocyclic compounds, may provide potential neuroprotective treatments for these diseases.
Article
Neurosciences
Raghavan Pillai Raju, Lun Cai, Alpna Tyagi, Subbiah Pugazhenthi
Summary: In this study, using RNA-seq analysis, we found significant changes in gene expression related to pathways including oxidation-reduction, oxidative phosphorylation, innate immune response, ribosomal protein synthesis, and ubiquitin proteosome system in the brains of 5XFAD mice. The downregulation of genes related to oxidation-reduction and upregulation of immune response genes were the most striking features observed. Gene interaction analysis revealed at least three distinct interaction clusters, with the predominant one relating to cellular energetics.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
German Plascencia-Villa, George Perry
Summary: The deterioration of brain cells in neurodegenerative diseases is accompanied by mitochondrial dysfunction. Current therapies for Alzheimer's and Parkinson's disease mainly focus on maintaining neurotransmitters and managing symptoms, with limited effectiveness in stopping or reversing the disease. This article discusses alternative molecular targets for treating neurodegeneration, such as regulating calcium ion transport, protein modification, glucose metabolism, antioxidants, metal chelators, vitamin supplementation, and mitochondrial transference. Some of these targeted therapies have shown promise in preclinical and animal studies, and are expected to have positive outcomes in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yunhui Cai, Ran Xiao, Yadan Zhang, Diya Xu, Ni Wang, Mengze Han, Yili Zhang, Lin Zhang, Wenhua Zhou
Summary: This study investigated the protective effect of 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on A beta((1-42))/Cu2+/AA mixture-treated SH-SY5Y cells through in vitro and in silico studies. The results showed that DHPA could inhibit oxidative stress, cell apoptosis, and mitochondrial damage, as well as activate the Keap1/Nrf2/HO-1 signaling pathway.
Article
Biochemistry & Molecular Biology
Kerry C. Ryan, Jocelyn T. Laboy, Kenneth R. Norman
Summary: Mitochondrial dysfunction and oxidative stress are major contributors to neurodegenerative diseases. This study reveals that elevated mitochondrial calcium levels, rather than cytosolic calcium levels, lead to increased reactive oxygen species (ROS) production and subsequent neurodegeneration in sel-12 mutants. The study also identifies mTORC1 signaling as a critical factor in sustaining high ROS levels in sel-12 mutants.
Article
Neurosciences
Irundika H. K. Dias, Hala Shokr, Freya Shephard, Lisa Chakrabarti
Summary: This study found that the metabolism of oxysterols is altered in the brain of Alzheimer's disease (AD) patients, leading to increased synthesis of 26-OHC, 25-OHC, and 7-oxocholesterol, and decreased levels of oxysterol sulfates. This may affect brain mitochondrial function and contribute to the progression of the disease.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Naoki Yoshida, Yugo Kato, Hirokatsu Takatsu, Koji Fukui
Summary: Many neurodegenerative disorders, including Alzheimer's disease (AD), are associated with oxidative damage accumulation. This study used transgenic mice as an AD model and found that cognitive impairment in AD mice occurs in an age-dependent manner. The hippocampus showed higher oxidative stress compared to other brain regions, potentially leading to mitochondrial dysfunction through oxidative damage.
Article
Cell Biology
Shanshan Wang, Taiga Ichinomiya, Yuki Terada, Dongsheng Wang, Hemal H. Patel, Brian P. Head
Summary: Mitochondrial dysfunction is a pivotal factor in Alzheimer's Disease, and the protein Cav-1 may play a critical role in maintaining normal mitochondrial morphology and function by regulating mitochondrial dynamics. Neuron-targeted expression of Cav-1 in PSAPP mice was shown to improve cognitive function, neuronal morphology, and synaptic structure, while also protecting mitochondrial function.
Review
Physiology
Tong Zhang, Minh D. A. Luu, Amalia M. M. Dolga, Ulrich L. M. Eisel, Martina Schmidt
Summary: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders worldwide, impacting millions of people's life expectancy and quality. Recent research suggests overlapping mechanisms may underlie AD and PD, with novel cell death mechanisms, such as parthanatos, netosis, lysosome-dependent cell death, senescence, and ferroptosis, being modulated by cAMP signaling via PKA and Epac. This review focuses on the overlapping mechanisms between AD and PD, specifically in relation to cAMP signaling and the pharmacology of cAMP signaling pathways.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Neurosciences
Milena Pinto, Francisca Diaz, Nadee Nissanka, Chelsey S. Guastucci, Placido Illiano, Roberta Brambilla, Carlos T. Moraes
Summary: Mitochondrial dysfunctions may not be the cause of amyloid accumulation in Alzheimer's disease. Inducing mitochondrial dysfunction in adult mice neurons resulted in mild oxidative stress but decreased amyloid pathology and altered amyloid precursor protein clearance pathway.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Geriatrics & Gerontology
Irene Costa-Laparra, Elena Juarez-Escoto, Carlos Vicario, Rosario Moratalla, Patricia Garcia-Sanz
Summary: Alzheimer's disease is characterized by memory loss and the presence of senile plaques and neurofibrillary tangles. This study investigates the impact of APOE ε4 and G206D-PSEN1 on the underlying mechanisms of Alzheimer's disease, including autophagy pathway and mitochondrial dysfunction.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Tiago Sousa, Paula I. Moreira, Susana Cardoso
Summary: Alzheimer's disease is a prevalent neurodegenerative disorder without an effective treatment. Dysfunction of mitochondria has been found in AD, and restoring their function may be a crucial strategy for tackling the disease.
Review
Biochemistry & Molecular Biology
Alpna Tyagi, Subbiah Pugazhenthi
Summary: SIRT3 is a mitochondrial deacetylase that regulates the functions of mitochondrial proteins. Its downregulation in neurodegenerative diseases is starting to be understood. SIRT3 plays a crucial role in brain energy metabolism and metabolic coupling. It is involved in the health benefits of lifestyle modifications and its deficiency is associated with metabolic syndrome. SIRT3 downregulation leads to mitochondrial dysfunction and inflammation, potentially contributing to Alzheimer's disease pathogenesis. This review discusses the roles of SIRT3 in brain physiology and pathology, as well as potential therapeutic agents for dementia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D'Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco, Vittorio Calabrese
Summary: Alzheimer's disease is the principal cause of dementia and is associated with neurodegenerative disorders. Hericium erinaceus, a nutritional mushroom with important antioxidant effects, has shown significant therapeutic effects in a rat model of AD, reducing behavioral changes and hippocampal neuronal degeneration.