RNA Modifications in Neurodegenerations

Calzoni, Eleonora; Argentati, Chiara; Cesaretti, Alessio; Montegiove, Nicolò; Tortorella, Ilaria; Bazzucchi, Martina; Morena, Francesco; Martino, Sabata; Emiliani, Carla

doi:10.1007/978-3-030-71612-7_2

Cited by 3 publications

(3 citation statements)

References 279 publications

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“…The most common neurodegenerative disorders are Parkinson's disease (PD), in which the loss of neurons in the basal ganglia leads to abnormal movement control, and Alzheimer's disease (AD), in which the degeneration of hippocampal and cortical neurons results in the loss of memory and cognitive abilities. However, there are a number of less common diseases, such as amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), which also represent severe and potentially fatal conditions [123]. The socio-economic impact of these highly disabling pathologies undoubtedly represents one of the most serious health problems of the millennium.…”

Section: Ntb Drug Delivery For the Treatment Of Neurological Diseasesmentioning

confidence: 99%

“…This is the case of levodopa, which, conveyed through this carrier, has provided a lasting recovery of motor function in the PD rat, or the bFGF which, administrated through PEG-PLGA composite NPs, has proved to determine an increase in cognitive abilities in AD models [129,130]. Neurodegenerative diseases also include lysosomal storage diseases (LSDs) caused by the absence or deficiency of specific enzymes of the lysosomal compartment that determine the accumulation of substrates in particular areas of the body, especially in the brain, resulting in a progressive loss of brain function and eventually death at a young age [3,48,49,123]. To date, for most LSDs, there are no definitive treatments other than palliative and supportive therapies, as the classic therapeutic approaches based on enzyme replacement therapy (ERT) and gene therapy (GT) usually fail to reach corrective levels of the deficient protein in the brain due to the insurmountable presence of the BBB.…”

Section: Ntb Drug Delivery For the Treatment Of Neurological Diseasesmentioning

confidence: 99%

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Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases

Montegiove

Calzoni

Emiliani

et al. 2022

JFB

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Diseases affecting the central nervous system (CNS) are among the most disabling and the most difficult to cure due to the presence of the blood–brain barrier (BBB) which represents an impediment from a therapeutic and diagnostic point of view as it limits the entry of most drugs. The use of biocompatible polymer nanoparticles (NPs) as vehicles for targeted drug delivery to the brain arouses increasing interest. However, the route of administration of these vectors remains critical as the drug must be delivered without being degraded to achieve a therapeutic effect. An innovative approach for the administration of drugs to the brain using polymeric carriers is represented by the nose-to-brain (NtB) route which involves the administration of the therapeutic molecule through the neuro-olfactory epithelium of the nasal mucosa. Nasal administration is a non-invasive approach that allows the rapid transport of the drug directly to the brain and minimizes its systemic exposure. To date, many studies involve the use of polymer NPs for the NtB transport of drugs to the brain for the treatment of a whole series of disabling neurological diseases for which, as of today, there is no cure. In this review, various types of biodegradable polymer NPs for drug delivery to the brain through the NtB route are discussed and particular attention is devoted to the treatment of neurological diseases such as Glioblastoma and neurodegenerative diseases.

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Section: Ntb Drug Delivery For the Treatment Of Neurological Diseasesmentioning

confidence: 99%

Section: Ntb Drug Delivery For the Treatment Of Neurological Diseasesmentioning

confidence: 99%

Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases

Montegiove

Calzoni

Emiliani

et al. 2022

JFB

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“…Almost all LSDs occur in childhood, with very few exceptions that can manifest at an older age. Some of these pathologies have been treated with Enzyme Replacement Therapy (ERT), others with Gene Therapy (GT), but a definitive therapy has not been found yet, because of the impossibility for recombinant enzymes or viral vectors to come across the Blood-Brain Barrier (BBB) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. The BBB has the task of maintaining cerebral homeostasis and protecting the CNS from the passage of potentially harmful substances, thus representing an almost insuperable barrier for the administration of pharmaceutical agents [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease

Calzoni

Cesaretti

Montegiove

et al. 2022

JFB

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Lysosomal storage disorders (LSDs) are a set of metabolic diseases caused by mutations in genes that are in charge of the production of lysosomal enzymes, resulting in the buildup of non-degraded substrates and the consequent systemic damage that mainly involves the Central Nervous System (CNS). One of the most widely used and studied treatments is Enzyme Replacement Therapy, which is based on the administration of the recombinant deficient enzyme. This strategy has often proved fallacious due to the enzyme instability in body fluids and its inability to reach adequate levels in the CNS. In this work, we developed a system based on nanotechnology that allows a stable enzyme to be obtained by its covalent immobilization on nanoparticles (NPs) of polylactic acid, subsequently administered to a cellular model of LSDs, i.e., Sandhoff disease, caused by the absence or deficiency of the β-d-N-acetyl-hexosaminidase A (HexA) enzyme. The HexA enzymes, loaded onto the polymeric NPs through an immobilization procedure that has already been investigated and validated, were found to be stable over time, maintain optimal kinetic parameters, be able to permeate the plasma membrane, hydrolyze HexA’s natural substrate, and restore enzyme activity close to the levels of healthy cells. These results thus lay the foundation for testing the HexA-NPs in animal models of the disease and thus obtaining an efficient drug-delivery system.

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Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis

Tortorella

Argentati

Emiliani

et al. 2022

Cells

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In this review, we shed light on recent advances regarding the characterization of biochemical pathways of cellular mechanosensing and mechanotransduction with particular attention to their role in neurodegenerative disease pathogenesis. While the mechanistic components of these pathways are mostly uncovered today, the crosstalk between mechanical forces and soluble intracellular signaling is still not fully elucidated. Here, we recapitulate the general concepts of mechanobiology and the mechanisms that govern the mechanosensing and mechanotransduction processes, and we examine the crosstalk between mechanical stimuli and intracellular biochemical response, highlighting their effect on cellular organelles’ homeostasis and dysfunction. In particular, we discuss the current knowledge about the translation of mechanosignaling into biochemical signaling, focusing on those diseases that encompass metabolic accumulation of mutant proteins and have as primary characteristics the formation of pathological intracellular aggregates, such as Alzheimer’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis and Parkinson’s Disease. Overall, recent findings elucidate how mechanosensing and mechanotransduction pathways may be crucial to understand the pathogenic mechanisms underlying neurodegenerative diseases and emphasize the importance of these pathways for identifying potential therapeutic targets.

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RNA Modifications in Neurodegenerations

Cited by 3 publications

References 279 publications

Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases

Biopolymer Nanoparticles for Nose-to-Brain Drug Delivery: A New Promising Approach for the Treatment of Neurological Diseases

HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease

Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis

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