Article
Neurosciences
Rodrigo S. Chaves, My Tran, Andrew R. Holder, Alexandra M. Balcer, Andrea M. Dickey, Elizabeth A. Roberts, Brian G. Bober, Edgar Gutierrez, Brian P. Head, Alex Groisman, Lawrence S. B. Goldstein, Angels Almenar-Queralt, Sameer B. Shah
Summary: Traumatic brain injury can increase the risk of developing sporadic Alzheimer's disease by causing aberrant accumulation of amyloid b peptide. However, the relationships among mTBI, amyloidogenesis, and axonal transport are still unclear.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Anusruti Sabui, Mitali Biswas, Pramod Rajaram Somvanshi, Preethi Kandagiri, Madhavi Gorla, Fareed Mohammed, Prasad Tammineni
Summary: Mitochondrial transport and distribution are altered in tauopathy neurons, with reduced anterograde transport and unchanged retrograde transport. The decrease in kinesin-mediated transport and the increase in dynein activity might contribute to the reduced axonal mitochondria in tauopathy neurons, thereby contributing to synaptic deficits in Alzheimer's disease and other tauopathies.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Review
Biochemistry & Molecular Biology
Kseniia S. Orobets, Andrey L. Karamyshev
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with age or inherited mutations. It is characterized by severe dementia that affects memory, cognitive functions, and daily life. The disease is linked to the accumulation of cytotoxic amyloid beta and hyperphosphorylated tau protein, as well as other pathological features. Various treatment options, such as antibody-based therapy and stem cell transplantation, are being investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Jinsu Park, Meenu Madan, Srinivasulu Chigurupati, Seung Hyun Baek, Yoonsuk Cho, Mohamed R. Mughal, Amin Yu, Sic L. Chan, Jogi Pattisapu, Mark P. Mattson, Dong-Gyu Jo
Summary: AQP1 levels are elevated in the cerebral cortex during the early stages of AD, particularly in vulnerable neurons, and increase as aging progresses in AD mouse models. AQP1 appears to reduce A beta production by inhibiting the binding between BACE1 and APP.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiaoling Liu, Yan Liu, Shangrong Ji
Summary: Alzheimer's disease is a common neurodegenerative disease that increases in prevalence with age. Studies suggest that abnormalities in the metabolism of APP are a major pathological feature of AD, with secretases playing a key role in APP processing. Research on secretases in the processing of APP could potentially lead to new directions for AD therapy.
Review
Neurosciences
Rebecca M. C. Gabriele, Emily Abel, Nick C. Fox, Selina Wray, Charles Arber
Summary: Amyloid precursor protein (APP) and its cleavage fragment Amyloid-beta (A beta) play crucial roles in Alzheimer's disease (AD). Genetic alterations that increase the overall dosage of APP or favor the generation of more aggregation-prone A beta species directly contribute to the disease. Lowering APP expression is an attractive approach for AD treatment and prevention. New technologies that reduce APP expression may offer disease modification and slow clinical progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Yoonsuk Cho, Han-Gyu Bae, Eitan Okun, Thiruma V. Arumugam, Dong-Gyu Jo
Summary: APP is an evolutionarily conserved transmembrane protein that serves as a precursor to amyloid-beta peptides, which are implicated in Alzheimer's disease. Studies have shown diverse pathological and physiological functions of APP and its cleavage products, but their roles are not fully understood. Current research focuses on APP processing and potential therapeutic approaches for Alzheimer's disease.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Cell Biology
Thomas D. D. Cushion, Ines Leca, David A. A. Keays
Summary: Microtubules are essential for various cellular functions and mutations in tubulin genes can lead to a range of diseases collectively known as tubulinopathies. Recent studies have shown that these mutations also affect microtubule-associated proteins (MAPs), which play important roles in microtubule regulation. In this review, we analyze the disease mechanisms caused by tubulin mutations on MAP binding and discuss how genetic variation can be utilized to identify novel MAPs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Christian Covill-Cooke, Viktoriya S. Toncheva, Josef T. Kittler
Summary: Peroxisomes are essential organelles involved in metabolic processes, requiring both long- and short-range trafficking for optimal positioning in cells. This review examines the mechanisms of peroxisomal distribution, with a focus on regulatory overlaps between mitochondrial and peroxisomal trafficking, as well as the role of mitochondrial Rho-GTPase Miro in peroxisomal dynamics. Additionally, it discusses pathological and pharmacological conditions affecting peroxisomal positioning, along with highlighting gaps in current knowledge and suggesting future research directions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Geriatrics & Gerontology
Kenji Yamamoto, Ryo Yamamoto, Nobuo Kato
Summary: In this study, it was found that specific antibodies can recover the activity of BK channels suppressed by Aβ oligomers in neurons of Alzheimer's disease model mice, suggesting an important role of APP in this process.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Neurosciences
Xi-Jun Song, He-Yan Zhou, Yu-Ying Sun, Han-Chang Huang
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. The main constituent of senile plaques, Aβ peptide, is derived from AβPP through cleaving by enzymes. Post-translational modifications like phosphorylation and glycosylation of AβPP may affect its trafficking and cleavage.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Review
Endocrinology & Metabolism
Yanjun Guo, Qinqiu Wang, Shenghui Chen, Chengfu Xu
Summary: This article summarizes the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues, indicating that peptides generated by non-amyloidogenic processing can have positive effects on metabolism, while those produced by amyloidogenic processing may have negative impacts. Abnormal expression of APP is associated with metabolic diseases (such as diabetes, obesity, etc.) and cancer.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Neurosciences
Dongjie Hu, Xiangjun Dong, Qunxian Wang, Mingjing Liu, Shuyue Luo, Zijun Meng, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: This study explores the role of Purkinje cell protein 4 (PCP4) in the progression of Alzheimer's disease (AD). PCP4 overexpression affects the processing of amyloid-beta protein precursor (AβPP) and promotes the production and deposition of amyloid-beta (Aβ). It also exacerbates learning and memory impairment in AD model mice. PCP4 may serve as a potential therapeutic target for AD by targeting Aβ pathology.
JOURNAL OF ALZHEIMERS DISEASE
(2023)