Abstract：
:Alzheimer's disease (AD) a neurodegenerative disorder of widely distributed cortical networks evolves over years while A beta (Aβ) oligomer neurotoxicity occurs within seconds to minutes. This disparity combined with disappointing outcomes of anti-amyloid clinical trials challenges the centrality of Aβ as principal mediator of neurodegeneration. Reconsideration of late life AD as the end-product of intermittent regional failure of the neuronal support system to meet the needs of vulnerable brain areas offers an alternative point of view. This model introduces four ideas: (1) That Aβ is a synaptic signaling peptide that becomes toxic in circumstances of metabolic stress. (2) That intense synaptic energy and maintenance requirements of cortical hubs may exceed resources during peak demand initiating a neurotoxic cascade in these selectively vulnerable regions. (3) That axonal transport to and from neuron soma cannot account fully for high mitochondrial densities and other requirements of distant terminal axons. (4) That neurons as specialists in information management, delegate generic support functions to astrocytes and other cell types. Astrocytes use intercellular transport by exosomes and tunneling nanotubes (TNTs) to deliver mitochondria, substrates and protein reprocessing services to axonal sites distant from neuronal soma. This viewpoint implicates the brain's support system and its disruption by various age and disease-related insults as significant mediators of neurodegenerative disease. A better understanding of this system should broaden concepts of neurodegeneration and facilitate development of effective treatments.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Engel PAdoi
10.1016/j.mehy.2014.10.013subject
Has Abstractpub_date
2014-12-01 00:00:00pages
802-8issue
6eissn
0306-9877issn
1532-2777pii
S0306-9877(14)00382-Xjournal_volume
83pub_type
杂志文章abstract：:Keratoacanthomas have many characteristics of squamous cell carcinoma and in the past were interpreted as squamous cell carcinomas. It is now known that these lesions spontaneously resolve if left untreated. In man the lesions occur on sunlight damaged areas or areas exposed to tar. Many of the experimental cancers of...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90063-1
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abstract：:Traumatic iris sphincter tear has been thought to occur secondary to anteroposterior compression of the globe with defined forces lead to equatorial expansion and active pull along the corneoscleral junction and sphincter tear. However, here in this report, we elaborate the additional forces involved in the traumatic ...
journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2019-01-01 00:00:00
abstract：:Preterm birth is an important perinatal health problem. Several possible mechanisms have been proposed but it may be important to have a testable mechanistic hypothesis that can explain the possible common mechanism for preterm births around the globe. Altered metabolism of micronutrients, like folic acid, vitamin B(1...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.08.001
更新日期：2011-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.08.047
更新日期：2007-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.03.042
更新日期：2011-07-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2019-09-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.10.015
更新日期：2011-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.12.022
更新日期：2004-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2013.09.032
更新日期：2013-12-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00363-8
更新日期：2003-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.04.011
更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00143-3
更新日期：2002-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0831
更新日期：2000-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.04.043
更新日期：2013-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90131-0
更新日期：1995-03-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1999.0979
更新日期：2000-06-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.10.005
更新日期：2013-12-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.06.023
更新日期：2011-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2008.11.022
更新日期：2009-04-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(95)90299-6
更新日期：1995-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2016.08.011
更新日期：2016-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.10.017
更新日期：2004-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.1998.0756
更新日期：1999-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
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更新日期：2012-06-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2010.02.031
更新日期：2010-08-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2014.07.015
更新日期：2014-10-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2000.1153
更新日期：2001-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(88)90093-x
更新日期：1988-07-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(02)00352-3
更新日期：2003-02-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.10.002
更新日期：2017-11-01 00:00:00
