Natural Products and Derivatives Affecting Neurotransmission Relevant to Alzheimer’s and Parkinson’s Disease

Abstract

The two major neurodegenerative diseases Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterised by low levels in the brain of the neurotransmitters acetylcholine (ACh) and dopamine (DA), respectively. Clinical treatment of these two conditions is palliative and relies, in most cases, on improving stimulation at the relevant receptors by either increasing levels of the endogenous neurotransmitter or by the use of substances which have a similar agonist response. Natural products continue to provide useful drugs in their own right but also provide templates for the development of other compounds. The major advances in the treatment of AD have been the use of acetylcholinesterase inhibitors such as galantamine, huperzine A, physostigmine and its derivatives to increase the levels of ACh rather than the use of cholinergic compounds, although compounds with nicotinic properties have attracted some interest. In contrast, the treatment of PD has relied on the elevation of DA levels by use of L-DOPA, its precursor, and by the administration of dopaminergic agonists, especially the ergot alkaloid derivatives. The use of inhibitors of enzymes that cause breakdown of DA is an avenue which is being explored. As well as the major natural products of clinical interest, the paper discusses the chemistry, activity and usage of the constituents of plants used in traditional medicine for the treatment of diseases presenting symptoms similar to those characteristic for Alzheimer’s or Parkinson’s disease.

<i>Gastrodia elata</i> modulates amyloid precursor protein cleavage and cognitive functions in mice

“…In traditional herbal medicine practice, synergistic and or antagonistic therapeutic efficacy among the herbs in any one prescription plays an important role in the treatment of illness. These observations may explain the medicinal effects related to AD and VD observed for Tianma and some other herbs (28)(29)(30)(31)(33)(34)(35)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). For instance, Gouteng has been traditionally used alongside with Tianma in treating high blood pressure (63).…”

Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression–Boldness Syndrome

“…To rule out a contribution of acetylcholine signaling to the spd behavioral phenotype, we treated homozygous spd mutants with a nonsedative dose (Fig. 8c) of the acetylcholinesterase inhibitor galantamine hydrochloride (Houghton and Howes, 2005) and measured aggression. Treatment with galantamine did not affect the aggression levels of either wild-type or mutant fish (Fig.…”

Monitoring enzyme reaction and screening of inhibitors of acetylcholinesterase by quantitative matrix-assisted laser desorption/ionization fourier transform mass spectrometry

“…To test whether the system was effective in a real screening experiment, an extract was made from Rhizoma Coptidis, which is a commonly used herb in Chinese medicine. Berberine, the representative quaternary ammonium alkaloid in commercial Rhizoma Coptidis, is an AChE inhibitor [42]. Three solvents were used to extract the active components from the dry powders of Rhizoma Coptidis.…”