VIP enhances phagocytosis of fibrillar beta-amyloid by microglia and attenuates amyloid deposition in the brain of APP/PS1 mice.

PloS One
Min SongYun Bai

Abstract

Vasoactive intestinal peptide (VIP) is a multifunctional neuropeptide with demonstrated immunosuppressive and neuroprotective activities. It has been shown to inhibit Amyloid beta (Aβ)-induced neurodegeneration by indirectly suppressing the production and release of a variety of inflammatory and neurotoxic factors by activated microglia. We demonstrated that VIP markedly increased microglial phagocytosis of fibrillar Aβ42 and that this enhanced phagocytotic activity depended on activation of the Protein kinase C (PKC) signaling pathway. In addition, VIP suppressed the release of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) from microglia activated by combined treatment with fibrillar Aβ42 and low dose interferon-γ (IFN-γ). We utilized an adenovirus-mediated gene delivery method to overexpress VIP constitutively in the hippocampus of APPswPS1 transgenic mice. The Aβ load was significantly reduced in the hippocampus of this animal model of Alzheimer's disease, possibly due to the accumulation and activation of cd11b-immunoactive microglial cells. The modulation of microglial activation, phagocytosis, and secretion by VIP is a promising therapeutic option for the treatment of Alzheimer's disease (AD).

References

Apr 15, 1992·Annals of the New York Academy of Sciences·D MuhvićS Efendić
Jul 1, 1995·Neurobiology of Aging·J N ZhouD F Swaab
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·I GozesD E Brenneman
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Jan 5, 2002·Neurobiology of Aging·G DiCarloD Morgan
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Carmen MartinezRosa P Gomariz
Mar 11, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mario Delgado, Doina Ganea
Apr 8, 2003·Current Pharmaceutical Design·A KrishnadasI Rubinstein
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sammy BedouiTakashi Yamamura
Nov 1, 2003·Science·Alon Monsonego, Howard L Weiner
Nov 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael C GrimmAndrew R Lloyd
May 26, 2004·Biochemical and Biophysical Research Communications·B M LoddeB J Baum
Jun 1, 2004·Pharmacological Reviews·Mario DelgadoDoina Ganea
May 23, 2009·Nature Reviews. Immunology·Serge Rivest
Jan 29, 2010·The New England Journal of Medicine·Henry W Querfurth, Frank M LaFerla
Mar 5, 2010·Fundamental & Clinical Pharmacology·Nada Choucair-JaafarJean-Pierre Gies
Mar 9, 2010·CNS & Neurological Disorders Drug Targets·Shweta Mandrekar-Colucci, Gary E Landreth

❮ Previous
Next ❯

Citations

Nov 14, 2013·The International Journal of Neuroscience·Jiaxiang XiongMiao Geng
Apr 9, 2013·Biochemical and Biophysical Research Communications·Jiong NiLimin Gu
Apr 12, 2012·Peptides·Ben-Shmuel SaritFleisher-Berkovich Sigal
Aug 15, 2015·Neural Plasticity·Stefano MoraraLuciano Provini
Jan 15, 2019·Current Pharmaceutical Design·Orhan Tansel Korkmaz, Neşe Tunçel
Sep 2, 2018·Journal of Neuroinflammation·Ana Rubio-AraizMarina A Lynch
Nov 14, 2013·Acta Neuropathologica·Stefan ProkopFrank L Heppner
Feb 6, 2017·Mediators of Inflammation·Lila CarnigliaMercedes Lasaga

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
PMA
ELISA
PCR
ELISAs
Protein Assay
fluorescence microscopy
enzyme-linked immunosorbent assay

Software Mentioned

SPSS
statistical for the social sciences
Image Pro Plus

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.