Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Cano, Amanda; Turowski, Patric; Ettcheto, Miren; Duskey, Jason Thomas; Tosi, Giovanni; Sánchez-López, Elena; García, María L.; Camins, Antoni; Souto, Eliana B.; Ruiz, Agustín; Marquié, Marta; Boada, Merçé

doi:10.1186/s12951-021-00864-x

Cited by 78 publications

(36 citation statements)

References 196 publications

(305 reference statements)

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“…Life expectancy has increased in recent decades, and it is expected to rise in the coming years [ 1 , 2 , 3 , 4 ]. Therefore, there is a higher probability of suffering from diseases related to an aging population, such as cardiovascular diseases [ 1 , 5 , 6 , 7 ], diabetes [ 7 , 8 , 9 ], hypertension [ 10 , 11 , 12 ], cancer [ 7 , 13 ], and neurological diseases [ 7 , 14 ]. Owing to the social, psychological, and economic conditions associated with aging, this has now become one of the major issues facing public health [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

Barragán

Ortega

Sorlí

et al. 2021

JCM

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Aging is a risk factor for several pathologies, restricting one’s health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.

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Section: Introductionmentioning

confidence: 99%

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

Barragán

Ortega

Sorlí

et al. 2021

JCM

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“…For such purpose, the biosafety of the nanoparticles is highly important. [ 46 ] To evaluate this, the nanoparticles were incubated with various types of cells, including human brain microvascular endothelial cells (HBMEC), human neuroblastoma SH‐SY5Y cells, SH‐SY5Y APPswe cells, and human astrocyte cell SVG P12 cells, and the potential cytotoxicity was measured via MTT assay. After 24 h incubation, all these cells remained > 90% viability with RDMR concentrations up to 800 × 10 −9 m ( Figure a, Figure S4a,d, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Brain‐Penetration and Neuron‐Targeting DNA Nanoflowers Co‐Delivering miR‐124 and Rutin for Synergistic Therapy of Alzheimer's Disease

Ouyang

Zhu

et al. 2022

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tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress, and neuroinflammatory response. [3] Among them, the amyloid theory that focuses on excessive deposition of β-amyloid (Aβ) has been extensively studied with wide acceptance. [4] In this theory, imbalance of Aβ metabolism and catabolism in the central nervous system (CNS) has been regarded as the main reason for AD-like pathology. [5] Aβ is the product of a proteolytic process of a transmembrane protein, amyloid precursor protein (APP), by β-secretase 1 (BACE1, β-site APP cleavage enzyme 1) and the γ-secretase. [6] The overgeneration and abnormal aggregation of Aβ 1-42 can cause the collapse of dendritic spines and neuronal loss, induce oxidative stress, and promote inflammatory by activating microglia, which in turn exacerbates the pathogenesis of AD. [7] Several strategies focus on blocking Aβ aggregation and alleviating Aβ-mediated neurotoxicity have been developed, including aggregation inhibition, copper chelation, Aβ photo-oxidation, fibril thermal dissociation, and Aβ degradation. [8] However, many Aβ targeting pharmacological treatments failed to slow down genitive decline or improve global functioning in phase 3 clinical trials although with definite efficacy at animal model. [9] Besides the pathological discrepancy between real clinical patient and AD animal model, [10] another important reason is that AD is a multifactorial disease and therapy targeting Aβ alone is far more enough. [11] Despite significant Alzheimer disease (AD) is the leading cause of dementia that affects millions of old people. Despite significant advances in the understanding of AD pathobiology, no disease modifying treatment is available. MicroRNA-124 (miR-124) is the most abundant miRNA in the normal brain with great potency to ameliorate AD-like pathology, while it is deficient in AD brain. Herein, the authors develop a DNA nanoflowers (DFs)-based delivery system to realize exogenous supplementation of miR-124 for AD therapy. The DFs with well-controlled size and morphology are prepared, and a miR-124 chimera is attached via hybridization. The DFs are further modified with RVG29 peptide to simultaneously realize brain-blood barrier (BBB) penetration and neuron targeting. Meanwhile, Rutin, a small molecular ancillary drug, is co-loaded into the DFs structure via its intercalation into the double stranded DNA region. Interestingly, Rutin could synergize miR-124 to suppress the expression of both BACE1 and APP, thus achieving a robust inhibition of amyloid β generation. The nanosystem could pro-long miR-124 circulation in vivo, promote its BBB penetration and neuron targeting, resulting in a significant increase of miR-124 in the hippocampus of APP/PS1 mice and robust therapeutic efficacy in vivo. Such a bio-derived therapeutic system shows promise as a biocompatible nanomedicine for AD therapy.

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“…In particular, the literature results of the last 20 years demonstrate NMeds intelligently designed to (1) improve the solubility of poorly soluble drugs [78,79], (2) stabilize and protect sensitive molecules such as proteins [80][81][82][83], peptides [84][85][86], and genetic material [87,88] from degradation, (3) promote their accumulation into target cells or tissues [89,90], and thereby (4) reduce drug toxicity outside the targeted tissue [91,92], and (5) prolong and/or control the release of the drug over time (Figure 1) [93][94][95][96]. All these properties together make NMeds perfect candidates for the treatment of a plethora of pathologies, especially those considered difficult to treat or that affect difficult-to-reach organs, including neurodegenerative disorders, such as Alzheimer's [97], Parkinson's [98], or Huntington's [99], different types of cancer [100], e.g., breast cancer [101], leukemia [102],…”

Section: Nanomedicinementioning

confidence: 99%

Tunneling Nanotubes: A New Target for Nanomedicine?

Ottonelli

Caraffi

Tosi

et al. 2022

IJMS

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Tunneling nanotubes (TNTs), discovered in 2004, are thin, long protrusions between cells utilized for intercellular transfer and communication. These newly discovered structures have been demonstrated to play a crucial role in homeostasis, but also in the spreading of diseases, infections, and metastases. Gaining much interest in the medical research field, TNTs have been shown to transport nanomedicines (NMeds) between cells. NMeds have been studied thanks to their advantageous features in terms of reduced toxicity of drugs, enhanced solubility, protection of the payload, prolonged release, and more interestingly, cell-targeted delivery. Nevertheless, their transfer between cells via TNTs makes their true fate unknown. If better understood, TNTs could help control NMed delivery. In fact, TNTs can represent the possibility both to improve the biodistribution of NMeds throughout a diseased tissue by increasing their formation, or to minimize their formation to block the transfer of dangerous material. To date, few studies have investigated the interaction between NMeds and TNTs. In this work, we will explain what TNTs are and how they form and then review what has been published regarding their potential use in nanomedicine research. We will highlight possible future approaches to better exploit TNT intercellular communication in the field of nanomedicine.

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Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Cited by 78 publications

References 196 publications

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

Brain‐Penetration and Neuron‐Targeting DNA Nanoflowers Co‐Delivering miR‐124 and Rutin for Synergistic Therapy of Alzheimer's Disease

Tunneling Nanotubes: A New Target for Nanomedicine?

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