PMID- 30420907
OWN - NLM
STAT- MEDLINE
DCOM- 20181213
LR  - 20181213
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2018
DP  - 2018
TI  - Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of 
      APP-CTFs in Alzheimer's Disease.
PG  - 2764831
LID - 10.1155/2018/2764831 [doi]
LID - 2764831
AB  - Vascular dysfunctions, hypometabolism, and insulin resistance are high and early 
      risk factors for Alzheimer's disease (AD), a leading neurological disease 
      associated with memory decline and cognitive dysfunctions. Early defects in 
      glucose transporters and glycolysis occur during the course of AD progression. 
      Hypometabolism begins well before the onset of early AD symptoms; this timing 
      implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 
      (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell 
      death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, 
      pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy 
      to the starving AD brain, a considerable energy crisis still persists and 
      increases during disease progression. Studies that track brain energy metabolism 
      in humans, animal models of AD, and in vitro studies reveal striking upregulation 
      of beta-amyloid precursor protein (beta-APP) and carboxy-terminal fragments (CTFs). 
      Currently, the precise role of CTFs is unclear, but evidence supports increased 
      endosomal-lysosomal trafficking of beta-APP and CTFs through autophagy through a 
      vague mechanism. While intracellular accumulation of Abeta is attributed as both the 
      cause and consequence of a defective endolysosomal-autophagic system, much 
      remains to be explored about the other beta-APP cleavage products. Many recent works 
      report altered amino acid catabolism and expression of several urea cycle enzymes 
      in AD brains, but the precise cause for this dysregulation is not fully 
      explained. In this paper, we try to connect the role of CTFs in the energy 
      translation process in AD brain based on recent findings.
FAU - Sivanesan, Senthilkumar
AU  - Sivanesan S
AUID- ORCID: 0000-0001-5133-7090
AD  - Department of Research and Development, Saveetha Institute of Medical and 
      Technical Sciences, Chennai 602 105, India.
FAU - Mundugaru, Ravi
AU  - Mundugaru R
AD  - Department of Research and Development, Saveetha Institute of Medical and 
      Technical Sciences, Chennai 602 105, India.
FAU - Rajadas, Jayakumar
AU  - Rajadas J
AUID- ORCID: 0000-0001-6520-3923
AD  - Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of 
      Medicine, Stanford, CA 94305, USA.
AD  - Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and 
      Medicine, University of California San Francisco, San Francisco, CA 94158, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20181021
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Amyloid beta-Protein Precursor)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Protein Precursor/*chemistry/*metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Endosomes/*metabolism
MH  - *Energy Metabolism
MH  - Humans
MH  - Lysosomes/*metabolism
PMC - PMC6215552
EDAT- 2018/11/14 06:00
MHDA- 2018/12/14 06:00
PMCR- 2018/10/21
CRDT- 2018/11/14 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2018/07/14 00:00 [revised]
PHST- 2018/08/19 00:00 [accepted]
PHST- 2018/11/14 06:00 [entrez]
PHST- 2018/11/14 06:00 [pubmed]
PHST- 2018/12/14 06:00 [medline]
PHST- 2018/10/21 00:00 [pmc-release]
AID - 10.1155/2018/2764831 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2018 Oct 21;2018:2764831. doi: 10.1155/2018/2764831. 
      eCollection 2018.