Abstract
The research progress of understanding the etiology and pathogenesis of Parkinson's disease (PD) has yet lead to the development of some clinical approaches intended to treat cognitive and behavioral symptoms, such as memory and perception disorders. Despite the major advances in different genetic causes and risk factors for PD, which share common pathways to cell dysfunction and death, there is not yet a complete model of PD that can be used to accurately predict the effect of drugs on disease progression. Clinical trials are also important to test any novel neuro-protective agent, and recently there have been great advances in the use of anti-inflammatory drugs and plant flavonoid antioxidants to protect against specific neuronal degeneration and its interference with lipid and cholesterol metabolism. The increasing knowledge of the molecular events underlying the degenerative process of PD has stimulated research to identify natural compounds capable of halting or slowing the progress of neural deterioration. Polyphenols and flavonoids, which play a neuroprotective role in a wide array of in vitro and in vivo models of neurological disorders, emerged from among the multi-target bio-agents found mainly in plants and microorganisms. This review presents a detailed overview of the multimodal activities of neuroprotective bio-agents tested so far, emphasizing their neurorescue/neuroregenerative activity. The brain-penetrating property of bioagents may make these compounds an important class of natural drugs for the treatment of neurodegenerative diseases. Although there are numerous studies demonstrating beneficial effects in the laboratory by identifying critical molecular targets, the clinical efficacy of these neuroprotective treatments remains to be proven accurately.
Keywords: Parkinson's disease, nutraceuticals, neuroprotection, phytobioactivity, degeneration, neuroscience.
Graphical Abstract
[http://dx.doi.org/dx.doi. org/10.1007/s12264-010-0302-z] [PMID: 20101274]
[http://dx.doi.org/ 10.3390/ijms18030551] [PMID: 28273839]
[http://dx.doi.org/dx. doi.org/10.1159/000470811] [PMID: 28738379]
[http://dx.doi.org/ dx.doi.org/10.1186/s40035-017-0096-2] [PMID: 29021896]
[http://dx.doi.org/dx. doi.org/10.3389/fneur.2011.00068] [PMID: 22125548]
[http://dx.doi.org/10.1002/med.21458] [PMID: 28697282]
[http://dx.doi.org/10.3389/fnins.2016.00026] [PMID: 26903794]
[http://dx.doi.org/10.1016/j.cell.2008.01.033] [PMID: 18295581]
[http://dx.doi.org/10.1016/j.nbd.2009.10.025] [PMID: 19900556]
[http://dx.doi.org/10.1002/ana.21995] [PMID: 20517933]
[http://dx.doi.org/10.1523/JNEUROSCI.20-13-05102.2000] [PMID: 10864967]
[http://dx.doi.org/dx. doi.org/10.1097/01.WCB.0000126563.85360.75] [PMID: 15362717]
[http://dx.doi.org/10.1212/WNL.0b013e318198 e0e9] [PMID: 19221312]
[http://dx.doi.org/10.1006/exnr.1994.1007] [PMID: 8307125]
[http://dx.doi.org/10.1046/j.1460-9568.2000.00901.x] [PMID: 10651888]
[http://dx.doi.org/10.1016/S0166-2236 (03)00038-9] [PMID: 12689773]
[http://dx.doi.org/10.3171/2016.2.FOCUS1688] [PMID: 27132522]
[http://dx.doi.org/10.1111/j.1749-6632.2001.tb03641.x] [PMID: 11462787]
[http://dx.doi.org/10.1016/j.nbd.2006.07.020] [PMID: 17055733]
[http://dx.doi.org/10.1007/s007020170018] [PMID: 11716151]
[http://dx.doi.org/10.1002/mds.26617] [PMID: 27030249]
[http://dx.doi.org/10.1016/j.neuroscience.2017. 10.018] [PMID: 29079063]
[http://dx.doi.org/10.1007/978-0-387-09550-9_7] [PMID: 18841705]
[http://dx.doi.org/ dx.doi.org/10.1007/s12017-016-8398-6] [PMID: 27147525]
[http://dx.doi.org/10.1111/j.1753-4887.2012.00484.x] [PMID: 22747840]
[http://dx.doi.org/dx. doi.org/10.1002/ptr.5622] [PMID: 27098287]
[http://dx.doi.org/10.1016/0304-3835(95)03964-X] [PMID: 7585479]
[http://dx.doi.org/10.1016/j.jtcme.2014.10.009] [PMID: 26151016]
[http://dx.doi.org/dx. doi.org/10.1191/0960327106ht589oa] [PMID: 16539212]
[http://dx.doi.org/10.2174/1871526514666140827 101901] [PMID: 25159304]
[http://dx.doi.org/10.1016/j.cbi.2015. 01.015] [PMID: 25637687]
[PMID: 20432629]
[http://dx.doi.org/10.1007/s10753-015-0128-y] [PMID: 25667012]
[PMID: 23638289]
[http://dx.doi.org/dx.doi. org/10.1016/j.foodchem.2005.11.020]
[http://dx.doi.org/dx. doi.org/10.1016/j.tice.2015.03.007] [PMID: 25891268]
[http://dx.doi.org/dx.doi. org/10.1016/j.neulet.2015.02.016] [PMID: 25681620]
[http://dx.doi.org/10.1016/j.ejphar.2010.09.003] [PMID: 20854811]
[http://dx.doi.org/10.2174/1570159 X16666180321095705] [PMID: 29564976]
[http://dx.doi.org/10.2174/138161212798918995] [PMID: 22211691]
[http://dx.doi.org/10. 2174/1570159X11311040002] [PMID: 24381528]
[http://dx.doi.org/10.1016/j.bcp.2009.03.031] [PMID: 19464433]
[http://dx.doi.org/10.1007/s10787-007-1614-0] [PMID: 18408903]
[http://dx.doi.org/dx. doi.org/10.1002/brb3.921] [PMID: 29484272]
[http://dx.doi.org/10.1186/s13024-015-0012-0] [PMID: 25888232]
[http://dx.doi.org/10.1046/j.1471-4159. 2003.02244.x] [PMID: 15009671]
[http://dx.doi.org/10.1089/can.2017.0002] [PMID: 28861502]
[http://dx.doi.org/ 10.1016/j.brainres.2006.11.063] [PMID: 17196181]
[http://dx.doi.org/10.1111/j.1476-5381.2008.00088.x] [PMID: 19220290]
[http://dx.doi.org/10.1136/archdischild-2014-306284] [PMID: 26063194]
[http://dx.doi.org/ dx.doi.org/10.1016/j.brainres.2012.02.058] [PMID: 22436849]
[http://dx.doi.org/10.1016/j.neuropharm. 2013.03.027] [PMID: 23587650]
[http://dx.doi.org/10.2174/092986706779026156] [PMID: 17168732]
[http://dx.doi.org/10.1021/jf010812u] [PMID: 11804508]
[http://dx.doi.org/10.1016/0140-6736(92)91277-F] [PMID: 1351198]
[http://dx.doi.org/10.1126/science. 275.5297.218] [PMID: 8985016]
[http://dx.doi.org/10.3390/ijms 19030652] [PMID: 29495357]
[http://dx.doi.org/10.1089/152308601317203567] [PMID: 11813979]
[http://dx.doi.org/10.1038/nrd2060] [PMID: 16732220]
[http://dx.doi.org/10. 1007/s00204-017-2073-z] [PMID: 28980048]
[http://dx.doi.org/10.1155/ 2015/730121] [PMID: 26681969]
[http://dx.doi.org/10.1016/j.neulet.2016.11.054] [PMID: 27894919]
[http://dx.doi.org/10.1016/j.cbi.2016.03.023] [PMID: 27016191]
[http://dx.doi.org/dx. doi.org/10.1007/s10059-013-2259-z] [PMID: 23456297]
[http://dx.doi.org/10.1016/j.biopha.2015.08.025] [PMID: 26349993]
[PMID: 24779896]
[http://dx.doi.org/10.3109/10717544.2014.885616] [PMID: 24512464]
[http://dx.doi.org/10. 1155/2015/392169] [PMID: 26180587]
[http://dx.doi.org/10.1016/j.pnpbp.2008.03.024] [PMID: 18471948]
[http://dx.doi.org/10.1523/JNEUROSCI.3442-11.2012] [PMID: 22219275]
[http://dx.doi.org/10.4103/0974-8490.157957] [PMID: 26130933]
[http://dx.doi.org/10.1016/j.jep. 2014.11.009] [PMID: 25449462]
[http://dx.doi.org/10.1155/2013/680545] [PMID: 24349614]
[http://dx.doi.org/10.1155/ 2018/7927568] [PMID: 29576855]
[http://dx.doi.org/10. 3233/RNN-150514] [PMID: 26409411]
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.02.027] [PMID: 19272442]
[http://dx.doi.org/10.4137/I MI.S25054] [PMID: 26604665]
[http://dx.doi.org/10.1089/ars. 1999.1.4-469] [PMID: 11233145]
[http://dx.doi.org/10.1142/S0192415X14500499] [PMID: 25004874]
[http://dx.doi.org/dx.doi. org/10.1111/j.1600-0404.1983.tb01516.x] [PMID: 6145282]
[http://dx.doi.org/10.1212/WNL.42.2.339] [PMID: 1736162]
[http://dx.doi.org/ 10.1042/bj3240025] [PMID: 9164836]
[http://dx.doi.org/dx.doi. org/10.1016/S0024-3205(99)00232-5] [PMID: 10416821]
[http://dx.doi.org/10.1111/j.1471-4159.2005.03000.x] [PMID: 15773909]
[http://dx.doi.org/10.1016/j.nut.2017.06.006] [PMID: 28935149]
[http://dx.doi.org/10.1186/s12937-016-0179-4] [PMID: 27268025]
[http://dx.doi.org/dx.doi. org/10.1007/s12017-016-8398-6] [PMID: 27147525]
[http://dx.doi.org/10.1517/13543776. 2014.995626] [PMID: 25535089]
[http://dx.doi.org/10.1016/B978-0-12-380860-8.00001-X] [PMID: 21310293]
[http://dx.doi.org/10.1523/JNEUROSCI. 0499-12.2012] [PMID: 23055502]
[http://dx.doi.org/10.1016/j.neurobiolaging. 2017.03.017] [PMID: 28407521]
[http://dx.doi.org/10.1016/S0161-813X (02)00079-7] [PMID: 12387363]
[PMID: 29363729]
[http://dx.doi.org/ 10.1007/978-3-319-18365-7_6] [PMID: 26092629]
[http://dx.doi.org/dx. doi.org/10.1056/NEJM196907312810517] [PMID: 5791298]
[http://dx.doi.org/10.12688/f1000 research.10100.1] [PMID: 28357055]
[http://dx.doi.org/10.1111/cns.12693] [PMID: 28371323]
[http://dx.doi.org/10.2174/0929867325666180410100559] [PMID: 29637853]
[http://dx.doi.org/10.2174/1381612823666170210143530] [PMID: 28190394]
[http://dx.doi.org/10.14218/JERP. 2016.00031]
[http://dx.doi.org/10.2174/1567205012666150713102326] [PMID: 26165866]
[http://dx.doi.org/10.1155/2016/7216912]