TY - JOUR
T1 - Potential application of lithium in Parkinson's and other neurodegenerative diseases
AU - Lazzara, Carol A.
AU - Kim, Yong Hwan
N1 - Publisher Copyright:
© 2015 Lazzara and Kim.
PY - 2015
Y1 - 2015
N2 - Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of a-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.
AB - Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of a-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.
KW - And autophagy
KW - Bcl-2
KW - Calpain
KW - GSK-3β
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=84946562056&partnerID=8YFLogxK
U2 - 10.3389/fnins.2015.00403
DO - 10.3389/fnins.2015.00403
M3 - Review article
AN - SCOPUS:84946562056
SN - 1662-4548
VL - 9
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - OCT
M1 - 403
ER -