The Glymphatic System: A Beginner’s Guide
TLDR
The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.Abstract:
The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.read more
Citations
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References
More filters
Journal ArticleDOI
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Journal ArticleDOI
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Warren J. Strittmatter,Ann M. Saunders,Donald E. Schmechel,Margaret A. Pericak-Vance,Jan J. Enghild,Guy S. Salvesen,Allen D. Roses +6 more
TL;DR: It is demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease.
Journal ArticleDOI
A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.
Jeffrey J. Iliff,Minghuan Wang,Minghuan Wang,Yonghong Liao,Benjamin A. Plogg,Weiguo Peng,Georg Andreas Gundersen,Helene Benveniste,G. Edward Vates,Rashid Deane,Steven A. Goldman,Erlend A. Nagelhus +11 more
TL;DR: An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.
Journal ArticleDOI
Sleep Drives Metabolite Clearance From the Adult Brain
Lulu Xie,Hongyi Kang,Qiwu Xu,Michael Chen,Yonghong Liao,Meenakshisundaram Thiyagarajan,John O’Donnell,Daniel J. Christensen,Charles Nicholson,Jeffrey J. Iliff,Takahiro Takano,Rashid Deane +11 more
TL;DR: It is reported that sleep has a critical function in ensuring metabolic homeostasis and convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep, suggesting the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
Journal ArticleDOI
Protein aggregation and neurodegenerative disease.
TL;DR: There is increased understanding of the pathways involved in protein aggregation, and some recent clues have emerged as to the molecular mechanisms of cellular toxicity, leading to approaches toward rational therapeutics.