PMID- 32340360
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 9
IP  - 4
DP  - 2020 Apr 23
TI  - Lymphocyte-Activation Gene 3 (LAG3) Protein as a Possible Therapeutic Target for 
      Parkinson's Disease: Molecular Mechanisms Connecting Neuroinflammation to 
      alpha-Synuclein Spreading Pathology.
LID - 10.3390/biology9040086 [doi]
LID - 86
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder 
      without any objective biomarker available to date. Increasing evidence highlights 
      the critical role of neuroinflammation, including T cell responses, and spreading 
      of aggregated alpha-synuclein in PD progression. Lymphocyte-activation gene 3 (LAG3) 
      belongs to the immunoglobulin (Ig) superfamily expressed by peripheral immune 
      cells, microglia and neurons and plays a key role in T cell regulation. The role 
      of LAG3 has been extensively investigated in several human cancers, whereas until 
      recently, the role of LAG3 in the central nervous system (CNS) has been largely 
      unknown. Accumulating evidence highlights the potential role of LAG3 in PD 
      pathogenesis, mainly by binding to alpha-synuclein fibrils and affecting its 
      endocytosis and intercellular transmission, which sheds more light on the 
      connection between immune dysregulation and alpha-synuclein spreading pathology. 
      Serum and cerebrospinal fluid (CSF) soluble LAG3 (sLAG3) levels have been 
      demonstrated to be potentially associated with PD development and clinical 
      phenotype, suggesting that sLAG3 could represent an emerging PD biomarker. 
      Specific single nucleotide polymorphisms (SNPs) of the LAG3 gene have been also 
      related to PD occurrence especially in the female population, enlightening the 
      pathophysiological background of gender-related PD clinical differences. Given 
      also the ongoing clinical trials investigating various LAG3-targeting strategies 
      in human diseases, new opportunities are being developed for PD treatment 
      research. In this review, we discuss recent preclinical and clinical evidence on 
      the role of LAG3 in PD pathogenesis and biomarker potential, aiming to elucidate 
      its underlying molecular mechanisms.
FAU - Angelopoulou, Efthalia
AU  - Angelopoulou E
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
FAU - Paudel, Yam Nath
AU  - Paudel YN
AUID- ORCID: 0000-0002-8804-6331
AD  - Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health 
      Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia.
FAU - Villa, Chiara
AU  - Villa C
AUID- ORCID: 0000-0003-2730-5974
AD  - School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
FAU - Shaikh, Mohd Farooq
AU  - Shaikh MF
AUID- ORCID: 0000-0001-9865-6224
AD  - Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health 
      Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia.
FAU - Piperi, Christina
AU  - Piperi C
AUID- ORCID: 0000-0002-2701-0618
AD  - Department of Biological Chemistry, Medical School, National and Kapodistrian 
      University of Athens, 11527 Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200423
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC7235703
OTO - NOTNLM
OT  - LAG3
OT  - Parkinson's disease
OT  - biomarker
OT  - neuroinflammation
OT  - alpha-synuclein
COIS- The authors declare no conflict of interest.
EDAT- 2020/04/29 06:00
MHDA- 2020/04/29 06:01
PMCR- 2020/04/01
CRDT- 2020/04/29 06:00
PHST- 2020/04/01 00:00 [received]
PHST- 2020/04/21 00:00 [revised]
PHST- 2020/04/22 00:00 [accepted]
PHST- 2020/04/29 06:00 [entrez]
PHST- 2020/04/29 06:00 [pubmed]
PHST- 2020/04/29 06:01 [medline]
PHST- 2020/04/01 00:00 [pmc-release]
AID - biology9040086 [pii]
AID - biology-09-00086 [pii]
AID - 10.3390/biology9040086 [doi]
PST - epublish
SO  - Biology (Basel). 2020 Apr 23;9(4):86. doi: 10.3390/biology9040086.