scholarly journals Alzheimer's Disease, Brain Injury, and C.N.S. Nanotherapy in Humans: Sonoporation Augmenting Drug Targeting

2017 ◽  
Author(s):  
Joseph S. D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Cell Types ◽  
Acoustic Power ◽  
Transcranial Ultrasound ◽  
Small Molecule Drug ◽  
Lipid Nanoemulsion ◽  
Cellular Types

Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

scholarly journals Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

2017 ◽  
Author(s):  
Joseph S. D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Cell Types ◽  
Acoustic Power ◽  
Transcranial Ultrasound ◽  
Small Molecule Drug ◽  
Lipid Nanoemulsion ◽  
Cellular Types

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

scholarly journals Nanotherapy for Early Dementia: Targeting Senile Endothelium

2017 ◽  
Author(s):  
Joseph S. D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Cell Types ◽  
Acoustic Power ◽  
Transcranial Ultrasound ◽  
Lipid Nanoemulsion ◽  
Early Dementia ◽  
Cellular Types

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

scholarly journals Nanotherapy for Early Dementia: Targeting Senile Dementia

2017 ◽  
Author(s):  
Joseph S. D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Senile Dementia ◽  
Cell Types ◽  
Acoustic Power ◽  
Transcranial Ultrasound ◽  
Lipid Nanoemulsion ◽  
Early Dementia

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

scholarly journals Astrocytic TSPO Upregulation Appears Before Microglial TSPO in Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1043-1056 ◽  
Author(s):  
Benjamin B. Tournier ◽  
Stergios Tsartsalis ◽  
Kelly Ceyzériat ◽  
Ben H. Fraser ◽  
Marie-Claude Grégoire ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Binding Sites ◽  
Temporal Cortex ◽  
Population Expansion ◽  
Cell Types ◽  
Translocator Protein ◽  
Cellular Origin

Background: In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-translocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation. Objective: The present study evaluates the cellular origin of TSPO alterations in Alzheimer’s disease (AD). Methods: The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects. Results: In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD. Conclusion: These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes.

scholarly journals In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1941 ◽  
Author(s):  
Benjamin B. Tournier ◽  
Stergios Tsartsalis ◽  
Kelly Ceyzériat ◽  
Valentina Garibotto ◽  
Philippe Millet
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Time Course ◽  
Single Photon ◽  
Photon Emission ◽  
Cell Types ◽  
Translocator Protein ◽  
Emission Computed Tomography ◽  
Cellular Origin

In the last decade, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in in vivo imaging has attempted to demonstrate the presence of neuroinflammatory reactions by measuring the 18 kDa translocator protein (TSPO) expression in many diseases of the central nervous system. We focus on two pathological conditions for which neuropathological studies have shown the presence of neuroinflammation, which translates in opposite in vivo expression of TSPO. Alzheimer’s disease has been the most widely assessed with more than forty preclinical and clinical studies, showing overall that TSPO is upregulated in this condition, despite differences in the topography of this increase, its time-course and the associated cell types. In the case of schizophrenia, a reduction of TSPO has instead been observed, though the evidence remains scarce and contradictory. This review focuses on the key characteristics of TSPO as a biomarker of neuroinflammation in vivo, namely, on the cellular origin of the variations in its expression, on its possible biological/pathological role and on its variations across disease phases.

scholarly journals Targeted Nanotherapy for Cognitive Impairment:  Blocking Amyloid-β-Induced Membrane Damage in Brain Tissue

2018 ◽  
Author(s):  
Joseph D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Subjects ◽  
Membrane Damage ◽  
Cell Types ◽  
Cubic Phase ◽  
Type I ◽  
Co Morbidity ◽  
Cns Penetration

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

scholarly journals BIOBASED NANOEMULSION FOR BLOCKING COVID-19 FROM ACCELERATING ALZHEIMER'S DISEASE

2021 ◽  
Vol 7 (4) ◽  
pp. 5-11
Author(s):  
J. S. D'Arrigo
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Cell Types ◽  
Competitive Binding ◽  
Amyloid A ◽  
Lipid Nanocarriers ◽  
Effective Therapeutic Strategy

An effective therapeutic strategy to delay dementia could be based upon nanotargeting drug(s), using lipid nanocarriers (<i>i.e.</i>, biobased nanoemulsion technology), toward a major serum amyloid A (SAA) receptor responsible for certain proinflammatory, SAA-mediated, cell signaling events. For example, other investigators have already confirmed that SR-BI receptors (or its human ortholog CLA-1) function as proinflammatory cell-surface SAA receptors, and additionally report that various ligands for CLA-1/SR-BI "efficiently compete" with SAA for CLA-1/SR-BI binding. A similar benefit (of "competitive binding") may well accompany the clinical intravenous use of the ("HDL-like") lipid nanocarriers (<i>i.e.</i>, biobased nanoemulsion [see above]), which have already been repeatedly described in the peer-reviewed literature as a targeted (and SR-BI mediated) drug-delivery agent. To conclude, the above-proposed "competitive binding", between SAA and such biobased nanoemulsion(s), could assist/enhance the protective (ordinarily anti-inflammatory) role of HDL - as well as provide targeted drug-delivery to the (human) brain cells bearing CLA-1/SR-BI receptors. The first resulting advantage is that this (intravenous) colloidal-nanocarrier therapeutic makes it possible for various cell types, all potentially implicated in Alzheimer's disease and/or (late-onset) dementia, to be simultaneously sought out and better reached for localized drug treatment of brain tissue <i>in vivo</i>. A second major advantage is that this therapeutic-target approach has particular relevance to the current COVID-19 human pandemic; namely, immune response and excessive inflammation in COVID-19 infection may accelerate the progression of brain inflammatory neurodegeneration which, if effectively halted, might play a major role in reducing Alzheimer's disease pathology.

scholarly journals Drug nanotargeting for treatment of neurodegeneration and aging

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Joseph S. D'Arrigo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Water Solubility ◽  
Drug Carrier ◽  
Cell Types ◽  
Integrative Approach ◽  
Cubic Phase ◽  
Type I ◽  
Natural Substances

Microvascular endothelial dysfunction precedes, often by decades, the cognitive decline associated with Alzheimer’s disease. Accordingly, cerebrovascular risk factors (e.g., atherosclerosis, diabetes, aging) contribute to the pathogenesis of this common neurodegenerative disease. By incorporating appropriate drug(s) into biobased (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier. This (intravenous) combination therapeutic, known to be a successful drug carrier, would make it possible for various cell types within the brain (all potentially implicated [see below] in Alzheimer’s disease) to be simultaneously nanotargeted for localized drug delivery via cell-surface SR-BI. Hence, such colloidal-nanocarrier targeting allows for various Alzheimer’s-related cell types to be simultaneously searched in a holistic integrative approach. This (colloidal-nanocarrier) targeting advantage, in vivo, may be particularly important when delivering pleiotropic natural substances (e.g., a flavonoid) or for repurposing an FDA-approved drug. For example, the described/proposed colloidal (nanoemulsion) nanocarrier is especially useful for the delivery of low-molecular-weight compounds having a significant degree of lipophilicity (i.e., low water solubility), such as various pleiotropic natural substances (e.g., the plant polyphenol known as “resveratrol”, commonly used as a dietary supplement).

Sign in / Sign up

Export Citation Format

Share Document