PMID- 33016916
OWN - NLM
STAT- MEDLINE
DCOM- 20210923
LR  - 20210923
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 82
IP  - s1
DP  - 2021
TI  - CDK5 Targeting as a Therapy for Recovering Neurovascular Unit Integrity in 
      Alzheimer's Disease.
PG  - S141-S161
LID - 10.3233/JAD-200730 [doi]
AB  - The neurovascular unit (NVU) is responsible for synchronizing the energetic 
      demand, vasodynamic changes, and neurochemical and electrical function of the 
      brain through a closed and interdependent interaction of cell components 
      conforming to brain tissue. In this review, we will focus on cyclin-dependent 
      kinase 5 (CDK5) as a molecular pivot, which plays a crucial role in the healthy 
      function of neurons, astrocytes, and the endothelium and is implicated in the 
      cross-talk of cellular adhesion signaling, ion transmission, and cytoskeletal 
      remodeling, thus allowing the individual and interconnected homeostasis of 
      cerebral parenchyma. Then, we discuss how CDK5 overactivation affects the 
      integrity of the NVU in Alzheimer's disease (AD) and cognitive impairment; we 
      emphasize how CDK5 is involved in the excitotoxicity spreading of glutamate and 
      Ca2+ imbalance under acute and chronic injury. Additionally, we present 
      pharmacological and gene therapy strategies for producing partial depletion of 
      CDK5 activity on neurons, astrocytes, or endothelium to recover neuroplasticity 
      and neurotransmission, suggesting that the NVU should be the targeted tissue unit 
      in protective strategies. Finally, we conclude that CDK5 could be effective due 
      to its intervention on astrocytes by its end feet on the endothelium and neurons, 
      acting as an intermediary cell between systemic and central communication in the 
      brain. This review provides integrated guidance regarding the pathogenesis of and 
      potential repair strategies for AD.
FAU - Posada-Duque, Rafael Andres
AU  - Posada-Duque RA
AD  - Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, 
      SIU, University of Antioquia, Medellin, Colombia.
AD  - Institute of Biology, Faculty of Exact and Natural Sciences, University of 
      Antioquia, Medellin, Colombia.
FAU - Cardona-Gomez, Gloria Patricia
AU  - Cardona-Gomez GP
AD  - Cellular and Molecular Neurobiology Area, Group of Neuroscience of Antioquia, 
      SIU, University of Antioquia, Medellin, Colombia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (CDK5 protein, human)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism/pathology
MH  - Clinical Trials as Topic/methods
MH  - Cyclin-Dependent Kinase 5/*antagonists & inhibitors/*metabolism
MH  - Drug Delivery Systems/*methods
MH  - Gene Silencing/drug effects/*physiology
MH  - Humans
MH  - Neurovascular Coupling/drug effects/*physiology
MH  - Protein Kinase Inhibitors/administration & dosage
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - CDK5
OT  - astrocytes
OT  - endothelium
OT  - neuroprotection
OT  - neurovascular unit
EDAT- 2020/10/06 06:00
MHDA- 2021/09/24 06:00
CRDT- 2020/10/05 12:09
PHST- 2020/10/06 06:00 [pubmed]
PHST- 2021/09/24 06:00 [medline]
PHST- 2020/10/05 12:09 [entrez]
AID - JAD200730 [pii]
AID - 10.3233/JAD-200730 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2021;82(s1):S141-S161. doi: 10.3233/JAD-200730.