Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM

Park, Min Hee; Lee, Ju Youn; Park, Kang Ho; Jung, In Kyung; Kim, Kyoung‐Tae; Lee, Yong Seok; Ryu, Hwa-Sung; Jeong, Yong Hoon; Kang, Minseok; Schwaninger, Markus; Gulbins, Erich; Reichel, Martin; Kornhuber, Johannes; Yamaguchi, Tomoyuki; Kim, Hee Jin; Kim, Seung Hyun; Schuchman, Edward H.; Jin, Hee Kyung; Bae, Jung Hoon

doi:10.1016/j.neuron.2018.09.010

Cited by 44 publications

(91 citation statements)

References 56 publications

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“…ASM can also be preferentially transported to the outer leaflet of the cell membrane and secreted into the extracellular space during cellular stress and disease 29,30 . Previous studies have reported that the expression and activity of ASM change with age [45][46][47] . Thus, in this section, we review the critical roles of ASM in association with aging-related dysfunctions in physiological processes.…”

Section: Role Of Asm In Agingmentioning

confidence: 96%

Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase

2020

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Aging, which is associated with age-related changes in physiological processes, is the most significant risk factor for the development and progression of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Accumulating evidence has indicated that sphingolipids are significant regulators that are associated with pathogenesis in aging and several age-related neurodegenerative diseases. In particular, abnormal levels of acid sphingomyelinase (ASM), one of the significant sphingolipid-metabolizing enzymes, have been found in the blood and some tissues under various neuropathological conditions. Moreover, recent studies have reported the importance of ASM as a critical mediator that contributes to pathologies in aging and age-related neurodegenerative diseases. In this review, we describe the pathophysiological processes that are regulated by ASM, focusing on the age-related neurodegenerative environment. Furthermore, we discuss novel insights into how new therapeutics targeting ASM may potentially lead to effective strategies to combat aging and age-related neurodegenerative diseases.

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Section: Role Of Asm In Agingmentioning

confidence: 96%

Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase

2020

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“…38 In addition, growing evidence has indicated that limited caveolae-mediated transcytosis maintains BBB integrity in the CNS, 44 and BBB disruption due to increased vesicle transport has been confirmed in many models. 27,45 Cav-1 is a major structural component of caveolae and is mainly expressed in the vessels of the CNS. 46 Umesalma et al reported that Ang Ⅱ increases the expression of Cav-1 in the CNS in hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…The BBB integrity assay was as previously described . Briefly, dextran （3 kDa, Invitrogen; D3328）was injected into the tail vein after 28 days.…”

Section: Methodsmentioning

confidence: 99%

“…The BBB integrity assay was as previously described. 27 Briefly, dextran (3 kDa, Invitrogen; D3328)was injected into the tail vein after 28 days. Two hours later, anesthetized mice were perfused with saline and 4% PFA, and brain tissues were then sectioned at a thickness of 30 μm for immunohistochemical staining.…”

Section: Bbb Integrity Assaymentioning

confidence: 99%

“…The Transmission electron microscopy (TEM) method was described in a previous study. 26,27 Mice were anesthetized with 1% pentobarbital sodium and perfused through the heart with 30 mL saline, followed by 1.25% glutaraldehyde and 2% PFA in 0.1 mol/L phosphate buffer (PB). Then, the brains were rapidly removed and postfixed for 3 days at 4°C.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

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Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

Chen

Wang

et al. 2020

CNS Neurosci Ther

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Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

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Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

Islam

Leach

Smith³

et al. 2021

Advanced Science

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The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood–brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed.

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Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM

Cited by 44 publications

References 56 publications

Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase

Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase

Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

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