Review
Pharmacology & Pharmacy
Tayebeh Noori, Ahmad Reza Dehpour, Antoni Sureda, Eduardo Sobarzo-Sanchez, Samira Shirooie
Summary: Negative psychological and physiological consequences of neurodegenerative disorders, especially Alzheimer's disease, affect millions of people globally. Current treatments focus on symptom management, with natural products showing promise in preventing and alleviating symptoms of AD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Food Science & Technology
Wenli Ruan, Shuoheng Shen, Yang Xu, Na Ran, Heng Zhang
Summary: As the global population ages, more patients are diagnosed with neurodegenerative diseases, for which curative drugs or treatments are still lacking. Procyanidins, found in plants like grapes, blackberries, and hawthorn leaves, show potential protective roles in reducing oxidative stress, inhibiting neuroinflammation, and decreasing abnormal protein aggregation in Alzheimer's disease, highlighting a promising new therapeutic strategy for neurodegenerative diseases.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biochemistry & Molecular Biology
Tetsuhito Nohara, Mayumi Tsuji, Tatsunori Oguchi, Yutaro Momma, Hideaki Ohashi, Miki Nagata, Naohito Ito, Ken Yamamoto, Hidetomo Murakami, Yuji Kiuchi
Summary: Amyloid-beta (A beta) is linked to Alzheimer's disease (AD) and causes nerve damage and neurotoxicity. AD is more common in women, who are more susceptible due to declining estrogen levels. Raloxifene, a selective estrogen receptor modulator, activates the GPER and protects against cognitive impairment. However, the effect of raloxifene on A beta-induced neurotoxicity remains uncertain. This study investigates the neuroprotective effects of raloxifene mediated by GPER against A beta-induced cytotoxicity.
Review
Biochemistry & Molecular Biology
Priyanka Rawat, Ujala Sehar, Jasbir Bisht, Ashley Selman, John Culberson, P. Hemachandra Reddy
Summary: This article summarizes the role of tau and phosphorylated tau (p-tau) in Alzheimer's disease (AD) and other tauopathies, highlighting current research on post-translational modifications and genetics of tau, tau pathology, the role of tau in tauopathies, and the development of new drugs targeting p-tau for therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Shiveena Bhatia, Rishi Rawal, Pratibha Sharma, Tanveer Singh, Manjinder Singh, Varinder Singh
Summary: Alzheimer's disease is a major cause of senile dementia, characterized by accumulation of plaques and tangles in the brain leading to neurodegeneration and cell death, along with other pathological features such as abnormal microvasculature and increased beta-amyloid production. Mitochondrial Dysfunction (MD) is implicated in all associated AD pathologies, with evidence suggesting its involvement in the progression of neurodegeneration in AD.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Cell Biology
Mahsa Pourhamzeh, Mohammad Taghi Joghataei, Soraya Mehrabi, Reza Ahadi, Seyed Mohammad Massood Hojjati, Nasrin Fazli, Seyed Massood Nabavi, Hossein Pakdaman, Koorosh Shahpasand
Summary: The research revealed the interplay between tauopathy and amyloidopathy processes in Alzheimer's disease. It was found that A beta(1-42) and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner. Tauopathy appears to be more distributable than amyloidopathy in the neurodegenerative disorder.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ruifeng Zhang, Miao Zeng, Xiaolu Zhang, Yujia Zheng, Nuan Lv, Luming Wang, Jiali Gan, Yawen Li, Xijuan Jiang, Lin Yang
Summary: Saponins, specifically ginsenoside Rg1 and pseudoginsenoside-F11, show the most promise in treating Alzheimer's disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. This review provides a comprehensive summary and classification of common saponins studied for their therapeutic potential in Alzheimer's disease, showcasing their underlying mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Liu Yang, Huimin Zhou, Lei Huang, Yong Su, Liangliang Kong, Pengmin Ji, Ran Sun, Chao Wang, Weiping Li, Weizu Li
Summary: Chronic glucocorticoid exposure can accelerate neuronal damage and beta-amyloid production by activating oxidative stress and NLRP1 inflammasome, leading to the deterioration of Alzheimer's disease. Inhibition of NLRP1 inflammasome may be an important strategy in improving chronic glucocorticoid-induced neuronal injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cell Biology
Yang You, Samuel W. Hersh, Roshanak Aslebagh, Scott A. Shaffer, Seiko Ikezu, Jesse Mez, Kathryn L. Lunetta, Mark W. Logue, Lindsay A. Farrer, Tsuneya Ikezu
Summary: In this study, the effects of a rare mutation in the AKAP9 gene on tau pathology and the tau interactome were investigated using CRISPR-Cas9 technology in SH-SY5Y P301L cells. The mutation was found to increase phosphorylated tau levels and alter tau-interacting proteins associated with RNA translation, RNA localization, and oxidative activity, which are consistent with previous findings in human AD brain samples. Functional studies further confirmed reduced protein synthesis activity and excessive oxidative stress in mutant cells, mimicking pathological phenotypes seen in AD.
Review
Geriatrics & Gerontology
Lan Zhang, Yiyuan Xia, Yuran Gui
Summary: The Apolipoprotein E (ApoE) gene, located on chromosome 19, is the most prevalent genetic risk factor for Alzheimer's disease (AD). The alleles e2, e3, and e4 of this gene give rise to the ApoE subtypes E2, E3, and E4, respectively. E2 and E4 are linked to increased plasma triglyceride concentrations and play a critical role in lipoprotein metabolism. Neuronal ApoE4 induces A beta and tau protein pathologies, leading to neuroinflammation and neuronal damage, impairing learning and memory functions. However, the mechanisms by which neuronal ApoE4 mediates AD pathology are still unclear. This review focuses on the pathophysiology of neuronal ApoE4 and its role in A beta deposition and tau protein hyperphosphorylation, providing potential therapeutic targets.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Neurosciences
Mahmoud B. Maina, Youssra K. Al-Hilaly, Louise C. Serpell
Summary: Oxidative stress contributes to aging and Alzheimer's disease by causing damage to proteins. The covalent links between adjacent tyrosines, known as dityrosine (DiY) cross-linking, can serve as a biomarker of accumulated oxidative stress. Studies have shown the presence of DiY crosslinks in both A beta and tau deposits, but there is no consensus on their impact on A beta and tau function, aggregation, and toxicity. This review summarizes the current understanding of the role of DiY on A beta and tau, and discusses its potential as a biomarker for Alzheimer's disease.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Oluwaseun Samuel Faborode, Ernest Dalle, Musa Vuyisile Mabandla
Summary: This study demonstrates that footshock stress can exacerbate Alzheimer's disease-like pathology, indicating a potential link between PTSD and dementia development. The research findings show that footshocks increase anxiety behavior, impair fear memory extinction, and induce oxidative stress and apoptosis in the amygdala and hippocampus.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Clinical Neurology
Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L. Forrest, Gabriella Chan, Julia van der Hoven, Annika van Hummel, Astrid F. Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G. Kovacs, Grant Morahan, Yazi D. Ke, Lars M. Ittner
Summary: In Alzheimer's disease, hyperexcitation of neuronal networks is an underlying disease mechanism. The study identifies LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations.
ACTA NEUROPATHOLOGICA
(2022)
Review
Biochemistry & Molecular Biology
Elena Tamagno, Michela Guglielmotto, Valeria Vasciaveo, Massimo Tabaton
Summary: The pathogenesis of Alzheimer's disease involves the accumulation of beta amyloid and vulnerability of the brain to oxidative stress, which are linked to each other. It is difficult to determine which comes first, Aβ or oxidative stress. Evidence suggests that oxidative stress occurs early in the development of Alzheimer's disease and plays a crucial role in the manifestation of clinical and pathological symptoms.
Review
Neurosciences
Musa O. Iliyasu, Sunday A. Musa, Sunday B. Oladele, Abdullahi I. Iliya
Summary: Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by tau pathology and accumulation of amyloid-beta (Aβ). Aβ aggregation leads to oxidative stress, inflammatory cascade, and caspase activation, causing hyperphosphorylation of tau protein and formation of neurofibrillary tangles (NFTs). Acetylcholine degradation is accelerated, resulting in neurotransmitter deficiency and cognitive impairment. AD research is necessary to identify novel compounds for treatment and prevention, including those targeting Aβ, tau, neurotransmitter modulation, neuroinflammation, neuroprotection, and cognition enhancement.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ivan Alic, Pollyanna A. Goh, Aoife Murray, Erik Portelius, Eleni Gkanatsiou, Gillian Gough, Kin Y. Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L. O'Brien, Jurgen Groet, Xiaowei Shao, Steven Havlicek, N. Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin, Sarah Hamburg, Margaret Phillips, Konstantin Pervushin, Mark Turmaine, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E. Martin, Jia Nee Foo, David L. Becker, Agueda Rostagno, Jorge Ghiso, Zeljka Krsnik, Goran Simic, Ivica Kostovi, Dinko Mitrecic, Paul T. Francis, Kaj Blennow, Andre Strydom, John Hardy, Henrik Zetterberg, Dean Nizetic
Summary: Research has shown that individuals with Down Syndrome exhibit Alzheimer's disease-like pathological changes, which can be successfully replicated in vitro cerebral organoids models. These findings suggest that DS cerebral organoids could serve as a potential detector for pre-morbid AD-risk populations, as well as a system for hypothesis-free drug screening and identification of natural suppressor genes for neurodegenerative diseases.
MOLECULAR PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Goran Simic, Vana Vukic, Janja Kopic, Zeljka Krsnik, Patrick R. Hof
Summary: The neural crest hypothesis suggests that the domestication syndrome's phenotypic features result from a reduction in neural crest cells or disruption in their migration. During evolution, humans underwent self-domestication, leading to the development of social abilities, language, and neoteny. Disorders in neural crest cell development can cause various conditions, but there is limited understanding for diseases related to characteristics of hyperdomestication or hypodomestication.
Article
Clinical Neurology
Mirjana B. Leko, Matea N. Perkovic, Gordana N. Erjavec, Natasa Klepac, Dubravka S. Strac, Fran Borovecki, Nela Pivac, Patrick R. Hof, Goran Simic
Summary: The study compared the association between MAOB rs1799836 polymorphism and APOE in AD, finding that the frequency of APOE epsilon 4/epsilon 4 homozygotes and APOE epsilon 4 carriers was significantly increased among patients carrying the AA MAOB rs1799836 genotype. Therefore, MAOB rs1799836 polymorphism may serve as a potential genetic biomarker of AD and a potential target for treatment.
CURRENT ALZHEIMER RESEARCH
(2021)
Article
Neurosciences
Mirjana Babic Leko, Jasna Jurasovic, Matea Nikolac Perkovic, Ena Spanic, Ankica Sekovanic, Tatjana Orct, Vesna Lukinovic Skudar, Koraljka Bacic Baronica, Spomenka Kidemet-Piskac, Zeljka Vogrinc, Nela Pivac, Fran Borovecki, Patrick R. Hof, Goran Simic
Summary: The study found that individuals with AD and carriers of the APOE ε4 allele had elevated levels of calcium, copper, and magnesium in plasma and CSF, while boron levels decreased. Therefore, further research on the association between essential metals and APOE should be continued both in vivo and in vitro.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Goran Simic, Zeljka Krsnik, Vinka Knezovic, Zlatko Kelovic, Mathias Lysholt Mathiasen, Alisa Junakovic, Milan Rados, Damir Mulc, Ena Spanic, Giulia Quattrocolo, Vanessa Jane Hall, Laszlo Zaborszky, Mario Vuksic, Francisco Olucha Bordonau, Ivica Kostovic, Menno P. Witter, Patrick R. Hof
Summary: The development of the human entorhinal cortex (EC), a major hub in the brain, has been analyzed in this study. The results show that the cytoarchitectural differentiation of the EC begins early in fetal development and follows a specific pattern. These findings have implications for understanding the normal function of the EC and its role in brain disorders.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Barbara Sitas, Mihaela Bobic-Rasonja, Goran Mrak, Sara Trnski, Magdalena Krbot Skoric, Darko Oreskovic, Vinka Knezovic, Zeljka Petelin Gadze, Zdravko Petanjek, Goran Simic, Danijela Kolenc, Natasa Jovanov Milosevic
Summary: This study evaluated the ECM profile of HS1 in drug-resistant MTLE patients and found changes in PNNs, ECM proteins, and glycosylation patterns associated with the condition. These findings suggest that ECM molecules and their modulators could be potential targets for developing new therapeutic approaches to drug-resistant epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ena Spanic, Lea Langer Horvat, Katarina Ilic, Patrick R. Hof, Goran Simic
Summary: Neuroinflammation is a key pathological feature of Alzheimer's disease (AD). This study demonstrates that NLRP1 inflammasome is more active in the AD brain and is positively correlated with the number of neurofibrillary tangles (NFTs), suggesting a causal link between neuroinflammation and neurofibrillary degeneration.
Article
Neurosciences
Goran Simic, Vana Vukic, Marija Babic, Maria Banovic, Ivana Berecic, Ena Spanic, Klara Zubcic, Anja Tea Golubic, Marija Barisic Kutija, Ana Merkler Sorgic, Zeljka Vogrinc, Ivan Lehman, Patrick R. Hof, Jadranka Sertic, Nina Barisic
Summary: This study aimed to identify reliable markers for monitoring treatment response and predicting treatment outcomes in patients with spinal muscular atrophy (SMA). The main finding was that the concentration of total tau protein in cerebrospinal fluid (CSF) correlated significantly with the duration of nusinersen treatment and motor improvement in SMA patients. The measurement of total tau concentration in CSF can serve as a reliable index for monitoring biomarker and clinical response to nusinersen therapy in SMA patients.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Mirjana Babic Leko, Matej Mihelcic, Jasna Jurasovic, Matea Nikolac Perkovic, Ena Spanic, Ankica Sekovanic, Tatjana Orct, Klara Zubcic, Lea Langer Horvat, Nikolina Pleic, Spomenka Kidemet-Piskac, Zeljka Vogrinc, Nela Pivac, Andrea Diana, Fran Borovecki, Patrick R. Hof, Goran Simic
Summary: Several metals, including heavy metals and essential metals, are associated with the pathogenesis of Alzheimer's disease. Further research is needed to understand the mechanisms of toxicity. This study found positive associations between levels of certain metals and AD biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mirjana Babic Leko, Matea Nikolac Perkovic, Ena Spanic, Dubravka Svob Strac, Nikolina Pleic, Zeljka Vogrinc, Ivana Gunjaca, Dora Bezovan, Gordana Nedic Erjavec, Natasa Klepac, Fran Borovecki, Tatijana Zemunik, Nela Pivac, Patrick R. Hof, Goran Simic
Summary: A decrease in serotonergic transmission and polymporphisms in serotonin receptor genes are associated with pathology, biomarkers, and cognitive abilities in Alzheimer's disease (AD), making them potential early genetic biomarkers of AD.
Article
Neurosciences
Klara Zubcic, Dina Franic, Mihaela Pravica, Patrick R. Hof, Goran Simic, Mirta Boban
Summary: This study investigated tau aggregation and toxicity under compromised protein homeostasis conditions. The results showed that human tau protein expressed in yeast did not lead to synthetic toxicity or obvious aggregate formation under mild proteotoxic stress or in mutants with impaired stress response pathways. These data suggest that human tau protein is not a major burden to the protein quality control system in yeast cells.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Mirjana Babic Leko, Lea Langer Horvat, Ena Spanic Popovacki, Klara Zubcic, Patrick R. Hof, Goran Simic
Summary: The role of metals in the pathogenesis of Alzheimer's disease (AD) is still unclear. Existing research has shown some associations between metal homeostasis and AD, but more studies are needed to understand this relationship. This review included human studies that examined metal concentrations in AD patients, investigated correlations between metal concentrations and AD biomarkers, and used Mendelian randomization to assess metal contributions to AD risk. Findings from individual studies on metal dynamics in dementia patients have been inconsistent, but there is some evidence suggesting that Zn levels decrease and Cu levels increase in AD patients. However, more research comparing metal and biomarker levels in AD patients is necessary. Furthermore, conducting additional Mendelian randomization studies with diverse ethnic backgrounds is critical to establish a causal relationship between metals and AD risk.
Article
Biochemistry & Molecular Biology
Lea Langer Horvat, Ena Spanic Popovacki, Mirjana Babic Leko, Klara Zubcic, Luka Horvat, Maja Mustapic, Patrick R. Hof, Goran Simic
Summary: The study found that both human tau oligomers and tau fibrils can rapidly propagate and induce tau-related changes, but with some differences in the spreading pattern and regions. Rats injected with human tau fibrils showed more severe tau protein changes after 4 months, which correlated well with cognitive impairment.
Review
Medicine, General & Internal
Marija Babic, Maria Banovic, Ivana Berecic, Tea Banic, Mirjana Babic Leko, Monika Ulamec, Alisa Junakovic, Janja Kopic, Jadranka Sertic, Nina Barisic, Goran Simic
Summary: Spinal muscular atrophy (SMA) is a rare genetic disorder caused by the deletion or mutation of the SMN1 gene. Nusinersen and risdiplam, the first FDA-approved medications, increase the production of SMN protein from the backup SMN2 gene. The search for prognostic and pharmacodynamic biomarkers in SMA patients' body fluids is ongoing, although more research is needed to identify new biomarkers or combinations of biomarkers.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Ena Spanic Popovacki, Mirjana Babic Leko, Lea Langer Horvat, Klara Brgic, Zeljka Vogrinc, Marina Boban, Natasa Klepac, Fran Borovecki, Goran Simic
Summary: This study aimed to determine the relationship between soluble TREM2 levels in cerebrospinal fluid (CSF) and plasma samples and other indicators of AD pathology. It was found that CSF sTREM2 levels were significantly correlated with neurofibrillary degeneration, cognitive decline, and inflammasome activity in AD patients. In addition, CSF sTREM2 levels could be used not only to distinguish between HC and AD patients but also as a biomarker to detect earlier changes in the MCI stage.
NEUROLOGY INTERNATIONAL
(2023)