Amyloid protein aggregates: new clients for mitochondrial energy production in the brain?

Alzheimer’s disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched ß-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to ß-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to a-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for ß-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.

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Neuroimaging in Alzheimer’s Disease

Bioinformatics ◽

10.4018/978-1-4666-3604-0.ch023 ◽

2013 ◽

pp. 427-431 ◽

Cited By ~ 1

Author(s):

Hidenao Fukuyama

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Posterior Part ◽

Lewy Body Disease ◽

New Drugs ◽

Amyloid Protein ◽

Dementia Patients ◽

Positron Emission ◽

Occipital Lobes ◽

The Brain

The diagnosis of Alzheimer’s disease (AD) is often based on clinical and pathological data. Positron emission tomography (PET) using the tracer 18F-FDG revealed findings specific to AD-mainly the posterior part of the brain and the association cortices of the parietal and occipital lobes were affected by a reduction in glucose metabolism. Recent advances in the development of tracers for amyloid protein, which is the key protein in the pathogenesis of AD, enables the pattern of deposition of amyloid protein in the brain to be visualized. Various tracers have been introduced to visualize other aspects of AD pathology. Recent clinical interests on dementia have focused on the early detection of AD and variation of Parkinson’s disease, namely dementia with Lewy body disease (DLB), because the earlier the diagnosis, the better the prognosis. The differential diagnosis of mild AD or mild cognitive impairment (MCI) as well as DLB has been studied using PET and MRI as part of the NIH’s Alzheimer disease Neuroimaging initiative (ADNI). At present, many countries are participating in the ADNI, which is yielding promising results. This chapter’s study will improve the development of new drugs for the treatment of dementia patients by enabling the evaluation of the effect and efficacy of those drugs.

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Colloidal-like aggregation of a functional amyloid protein

Physical Chemistry Chemical Physics ◽

10.1039/d0cp03265d ◽

2020 ◽

Vol 22 (40) ◽

pp. 23286-23294

Author(s):

David N. Azulay ◽

Mnar Ghrayeb ◽

Ilanit Bensimhon Ktorza ◽

Ido Nir ◽

Rinad Nasser ◽

...

Keyword(s):

Protein Aggregates ◽

Amyloid Protein ◽

Functional Amyloid ◽

Acidic Conditions

TasA, a bacterial functional amyloid protein, aggregates in a colloidal – like mechanism upon exposure to acidic conditions.

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Methylpiperidinopyrazole Attenuates Estrogen-Induced Mitochondrial Energy Production and Subsequent Osteoblast Maturation via an Estrogen Receptor Alpha-Dependent Mechanism

Molecules ◽

10.3390/molecules25122876 ◽

2020 ◽

Vol 25 (12) ◽

pp. 2876

Author(s):

Poh-Shiow Yeh ◽

Jui-Tai Chen ◽

Yih-Giun Cherng ◽

Shun-Tai Yang ◽

Yu-Ting Tai ◽

...

Keyword(s):

Energy Production ◽

Estrogen Receptor Alpha ◽

Type I Collagen ◽

Atp Synthesis ◽

Neonatal Rat ◽

Type I ◽

Collagen Mrna ◽

Adenosine Phosphate ◽

Mitochondrial Energy Production ◽

Osteoblast Maturation

An estrogen deficiency is the main cause of osteoporosis in postmenopausal women. In bone remodeling, estrogen receptors (ERs) can mediate estrogen-transducing signals. Methylpiperidinopyrazole (MPP) is a highly specific antagonist of ER-alpha (ERα). This study was designed to evaluate the effects of MPP on estrogen-induced energy production, subsequent osteoblast maturation, and the possible mechanisms. Exposure of primary osteoblasts isolated from neonatal rat calvarias to MPP did not affect cell morphology or survival. Estradiol can induce translocation of ERα into mitochondria from the cytoplasm. Interestingly, pretreatment of rat calvarial osteoblasts with MPP lowered estrogen-induced ERα translocation. Sequentially, estrogen-triggered expressions of mitochondrial energy production-linked cytochrome c oxidase (COX) I and COX II messenger (m)RNAs were inhibited following pretreatment with MPP. Consequently, MPP caused decreases in estrogen-triggered augmentation of the activities of mitochondrial respiratory complex enzymes and levels of cellular adenosine phosphate (ATP). During progression of osteoblast maturation, estrogen induced bone morphogenetic protein (BMP)-6 and type I collagen mRNA expressions, but MPP treatment inhibited such induction. Consequently, estrogen-induced osteoblast activation and mineralization were attenuated after exposure to MPP. Taken together, MPP suppressed estrogen-induced osteoblast maturation through decreasing chromosomal osteogenesis-related BMP-6 and type I collagen mRNA expressions and mitochondrial ATP synthesis due to inhibiting energy production-linked COX I and II mRNA expressions. MPP can appropriately be applied to evaluate estrogen-involved bioenergetics and osteoblast maturation.

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Extracellular Vesicles in Alzheimer’s and Parkinson’s Disease: Small Entities with Large Consequences

Cells ◽

10.3390/cells9112485 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2485

Author(s):

Charysse Vandendriessche ◽

Arnout Bruggeman ◽

Caroline Van Cauwenberghe ◽

Roosmarijn E. Vandenbroucke

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Progression ◽

Extracellular Vesicles ◽

Neurodegenerative Disorders ◽

Neuronal Damage ◽

Protein Aggregates ◽

Pathological Changes ◽

Associated Proteins ◽

The Brain

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are incurable, devastating neurodegenerative disorders characterized by the formation and spreading of protein aggregates throughout the brain. Although the exact spreading mechanism is not completely understood, extracellular vesicles (EVs) have been proposed as potential contributors. Indeed, EVs have emerged as potential carriers of disease-associated proteins and are therefore thought to play an important role in disease progression, although some beneficial functions have also been attributed to them. EVs can be isolated from a variety of sources, including biofluids, and the analysis of their content can provide a snapshot of ongoing pathological changes in the brain. This underlines their potential as biomarker candidates which is of specific relevance in AD and PD where symptoms only arise after considerable and irreversible neuronal damage has already occurred. In this review, we discuss the known beneficial and detrimental functions of EVs in AD and PD and we highlight their promising potential to be used as biomarkers in both diseases.

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Environmental and Nutritional “Stressors” and Oligodendrocyte Dysfunction: Role of Mitochondrial and Endoplasmatic Reticulum Impairment

Biomedicines ◽

10.3390/biomedicines8120553 ◽

2020 ◽

Vol 8 (12) ◽

pp. 553

Author(s):

Jessica Maiuolo ◽

Micaela Gliozzi ◽

Vincenzo Musolino ◽

Cristina Carresi ◽

Saverio Nucera ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Energy Production ◽

Lipid Synthesis ◽

Main Function ◽

Cellular Functions ◽

Mitochondrial Oxidative Stress ◽

The Central Nervous System ◽

Altered Regulation ◽

The Brain

Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.

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