Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.27 (AMPK)
 6,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress-mediated neurodegeneration is responsible for 12% mortality around the globe. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are the most prevalent neurodegenerative diseases, associated with modulation of acetylcholine levels and amyloid beta accumulation & dopamine level and alpha-synuclein oligomerization, respectively. Therefore, a better understanding of their pathological mechanisms reveals novel target proteins and encourages exploitation of suitable lead molecules. In the present study, targets for AD and PD were sought not only to suppress the pathological condition but to restore the normal physiological function. In this view, activation of retinoic acid receptor alpha can be formulated as a novel target to improve choline acetyltransferase transcription that works together with acetylcholine esterase and beta-secretase 1 inhibition against AD. Likewise, inhibition of Polo-like kinase 2 fails to phosphorylate alpha-synuclein and motivates efficient autophagic clearance. Therefore, PLK2 inhibition, together with L-DOPA supplementation and monoamine oxidase B inhibition widens the therapeutic options for PD. As oxidative stress is the major factor for neurodegeneration, AMPK activation stabilizes energy metabolism and Sirtuin 1 (histone deacetylase 1) activation enhances AMPK, PGC1a and Nrf gene expressions. Phytochemical extracts from saffron stigma were broadly appreciated on memory enhancement and cognition. However, the exact mechanism was not established. Therefore, this inspires the exploitation of phytochemicals in saffron stigma extract using in-silico tools, to anticipate lead molecules that interact with various neurodegeneration associated protein targets.
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PMID:Multifaceted targeting of neurodegeneration with bioactive molecules of saffron (Crocus sativus): An insilco evidence-based hypothesis. 3247 Jul 90

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes. We previously showed that co-treatment with metformin and 3,4-dihydroxyphenyl-l-alanine (l-DOPA) prevented the development of l-DOPA-induced dyskinesia in a 6-hydroxydopamine (6-OHDA)-lesioned animal model of PD. However, effects of metformin on PD- and aging-induced genes in reactive astrocytes remain unknown. In this study, we assessed the effect of metformin on motor function, neuroprotection, and reactive astrocytes in the 6-OHDA-induced PD animal model. In addition, the effects of metformin on the genes expressed by specific types of astrocytes were analyzed in PD model and aged mice. Here, we showed that metformin treatment effectively improves the motor symptoms in the 6-OHDA-induced PD mouse model, whereas metformin had no effect on tyrosine hydroxylase-positive neurons. The activation of AMPK and BDNF signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum. Metformin treatment caused astrocytes to alter reactive genes in a PD animal model. Moreover, aging-induced genes in reactive astrocytes were effectively regulated or suppressed by metformin treatment. Taken together, these results suggest that metformin should be evaluated for the treatment of Parkinson's disease and related neurologic disorders characterized by astrocyte activation.
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PMID:Metformin regulates astrocyte reactivity in Parkinson's disease and normal aging. 3249 90