PMID- 31584139
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 40
IP  - 3
DP  - 2020 Apr
TI  - Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in 
      Neurodegeneration.
PG  - 313-345
LID - 10.1007/s10571-019-00741-0 [doi]
AB  - Neurodegeneration entails progressive loss of neuronal structure as well as 
      function leading to cognitive failure, apathy, anxiety, irregular body movements, 
      mood swing and ageing. Proteomic dysregulation is considered the key factor for 
      neurodegeneration. Mechanisms involving deregulated processing of proteins such 
      as amyloid beta (Abeta) oligomerization; tau hyperphosphorylation, prion misfolding; 
      alpha-synuclein accumulation/lewy body formation, chaperone deregulation, 
      acetylcholine depletion, adenosine 2A (A2A) receptor hyperactivation, secretase 
      deregulation, leucine-rich repeat kinase 2 (LRRK2) mutation and mitochondrial 
      proteinopathies have deeper implications in neurodegenerative disorders. Better 
      understanding of such pathological mechanisms is pivotal for exploring crucial 
      drug targets. Herein, we provide a comprehensive outlook about the diverse 
      proteomic irregularities in Alzheimer's, Parkinson's and Creutzfeldt Jakob 
      disease (CJD). We explicate the role of key neuroproteomic drug targets notably 
      Abeta, tau, alpha synuclein, prions, secretases, acetylcholinesterase (AchE), LRRK2, 
      molecular chaperones, A2A receptors, muscarinic acetylcholine receptors (mAchR), 
      N-methyl-D-aspartate receptor (NMDAR), glial cell line-derived neurotrophic 
      factor (GDNF) family ligands (GFLs) and mitochondrial/oxidative stress-related 
      proteins for combating neurodegeneration and associated cognitive and motor 
      impairment. Cross talk between amyloidopathy, synucleinopathy, tauopathy and 
      several other proteinopathies pinpoints the need to develop safe therapeutics 
      with ability to strike multiple targets in the aetiology of the neurodegenerative 
      disorders. Therapeutics like microtubule stabilisers, chaperones, kinase 
      inhibitors, anti-aggregation agents and antibodies could serve promising regimens 
      for treating neurodegeneration. However, drugs should be target specific, safe 
      and able to penetrate blood-brain barrier.
FAU - Dar, Khalid Bashir
AU  - Dar KB
AD  - Department of Clinical Biochemistry, Faculty of Biological Sciences, University 
      of Kashmir, Srinagar, India.
AD  - Department of Biochemistry, Faculty of Biological Sciences, University of 
      Kashmir, Srinagar, India.
FAU - Bhat, Aashiq Hussain
AU  - Bhat AH
AD  - Department of Clinical Biochemistry, Faculty of Biological Sciences, University 
      of Kashmir, Srinagar, India.
AD  - Department of Biochemistry, Faculty of Biological Sciences, University of 
      Kashmir, Srinagar, India.
FAU - Amin, Shajrul
AU  - Amin S
AD  - Department of Biochemistry, Faculty of Biological Sciences, University of 
      Kashmir, Srinagar, India.
FAU - Reshi, Bilal Ahmad
AU  - Reshi BA
AD  - Department of Biotechnology, Faculty of Biological Sciences, University of 
      Kashmir, Srinagar, India.
FAU - Zargar, Mohammad Afzal
AU  - Zargar MA
AD  - Department of Clinical Biochemistry, Faculty of Biological Sciences, University 
      of Kashmir, Srinagar, India.
FAU - Masood, Akbar
AU  - Masood A
AD  - Department of Biochemistry, Faculty of Biological Sciences, University of 
      Kashmir, Srinagar, India.
FAU - Ganie, Showkat Ahmad
AU  - Ganie SA
AUID- ORCID: 0000-0001-6295-4959
AD  - Department of Clinical Biochemistry, Faculty of Biological Sciences, University 
      of Kashmir, Srinagar, India. showkatganie@kashmiruniversity.ac.in.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191004
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Proteome)
SB  - IM
MH  - Alzheimer Disease/metabolism/pathology/physiopathology
MH  - Animals
MH  - Creutzfeldt-Jakob Syndrome/metabolism/pathology/physiopathology
MH  - Humans
MH  - *Molecular Targeted Therapy/methods/trends
MH  - Nerve Degeneration/genetics/*metabolism/pathology
MH  - Parkinson Disease/metabolism/pathology/physiopathology
MH  - Protein Aggregation, Pathological/genetics/*metabolism/physiopathology/therapy
MH  - Proteome/*analysis/metabolism
MH  - Proteomics
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - Chaperones
OT  - Drug targets
OT  - Free radicals
OT  - Mitophagy
OT  - Neurodegeneration
EDAT- 2019/10/05 06:00
MHDA- 2020/12/15 06:00
CRDT- 2019/10/05 06:00
PHST- 2019/05/13 00:00 [received]
PHST- 2019/08/06 00:00 [accepted]
PHST- 2019/10/05 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2019/10/05 06:00 [entrez]
AID - 10.1007/s10571-019-00741-0 [pii]
AID - 10.1007/s10571-019-00741-0 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2020 Apr;40(3):313-345. doi: 10.1007/s10571-019-00741-0. Epub 
      2019 Oct 4.