PMID- 25426138
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141126
LR  - 20200930
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 5
DP  - 2014
TI  - Phosphatases of alpha-synuclein, LRRK2, and tau: important players in the 
      phosphorylation-dependent pathology of Parkinsonism.
PG  - 382
LID - 10.3389/fgene.2014.00382 [doi]
LID - 382
AB  - An important challenge in the field of Parkinson's disease (PD) is to develop 
      disease modifying therapies capable of stalling or even halting disease 
      progression. Coupled to this challenge is the need to identify disease 
      biomarkers, in order to identify pre-symptomatic hallmarks of disease and monitor 
      disease progression. The answer to these challenges lies in the elucidation of 
      the molecular causes underlying PD, for which important leads are disease genes 
      identified in studies investigating the underlying genetic causes of PD. LRRK2 
      and alpha-syn have been both linked to familial forms of PD as well as associated to 
      sporadic PD. Another gene, microtubule associated protein tau (MAPT), has been 
      genetically linked to a dominant form of frontotemporal dementia and parkinsonism 
      linked to chromosome 17 (FTDP-17) and genome-wide association studies report a 
      strong association between MAPT and sporadic PD. Interestingly, LRRK2, alpha-syn, and 
      tau are all phosphorylated proteins, and their phosphorylation patterns are 
      linked to disease. In this review, we provide an overview of the evidence linking 
      LRRK2, alpha-syn, and tau phosphorylation to PD pathology and focus on studies which 
      have identified phosphatases responsible for dephosphorylation of 
      pathology-related phosphorylations. We also discuss how the LRRK2, alpha-syn, and tau 
      phosphatases may point to separate or cross-talking pathological pathways in PD. 
      Finally, we will discuss how the study of phosphatases of dominant Parkinsonism 
      proteins opens perspectives for targeting pathological phosphorylation events.
FAU - Taymans, Jean-Marc
AU  - Taymans JM
AD  - Department of Neurosciences, Laboratory for Neurobiology and Gene Therapy, KU 
      Leuven Leuven, Belgium.
FAU - Baekelandt, Veerle
AU  - Baekelandt V
AD  - Department of Neurosciences, Laboratory for Neurobiology and Gene Therapy, KU 
      Leuven Leuven, Belgium.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20141107
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC4224088
OTO - NOTNLM
OT  - LRRK2
OT  - PP1
OT  - PP2A
OT  - Parkinson disease
OT  - alpha-synuclein
OT  - phosphatase
OT  - phosphorylation
OT  - tau proteins
OT  - tauopathies
EDAT- 2014/11/27 06:00
MHDA- 2014/11/27 06:01
PMCR- 2014/11/07
CRDT- 2014/11/27 06:00
PHST- 2014/06/21 00:00 [received]
PHST- 2014/10/17 00:00 [accepted]
PHST- 2014/11/27 06:00 [entrez]
PHST- 2014/11/27 06:00 [pubmed]
PHST- 2014/11/27 06:01 [medline]
PHST- 2014/11/07 00:00 [pmc-release]
AID - 10.3389/fgene.2014.00382 [doi]
PST - epublish
SO  - Front Genet. 2014 Nov 7;5:382. doi: 10.3389/fgene.2014.00382. eCollection 2014.