Hydroxytyrosol improves the mitochondrial energetic deficit in a cellular model of Alzheimer’s disease. – Science & Wine
By Emma Burgos-Ramos Mitochondrial energy deficit is one of the hallmarks of neurodegenerative disorders, for example Alzheimer's disease (AD). AD is one of the main diseases associated with aging whose prevalence increases from the age of 65: around 46.8 million people worldwide are affected by AD and this number will triple by 2050 [1]. Therefore, […]

By Emma Burgos-Ramos

Mitochondrial energy deficit is one of the hallmarks of neurodegenerative disorders, for example Alzheimer's disease (AD). AD is one of the main diseases associated with aging whose prevalence increases from the age of 65: around 46.8 million people worldwide are affected by AD and this number will triple by 2050 [1]. Therefore, it is essential to elucidate the pathophysiology of AD in order to design new strategies to prevent, attenuate and / or delay the development of AD. AD is characterized by irreversible memory loss, in part triggered by the formation of senile extracellular plaques, accumulations of amyloid peptide β (Aβ), and intracellular neurofibrillary tangles of hyperphophorylated tau protein, which negatively affect synaptogenesis [2]. This dynamic neurobiological process depends on high levels of energy, supplied by the mitochondria. Specifically, the greatest amount of cellular adenosine triphosphate (ATP) comes from the mitochondrial electron transport chain.

Adherence to a Mediterranean diet is associated with a lower incidence of cognitive decline, and AD and extra virgin olive oil (poly) phenols such as oleuropein and hydroxytyrosol (HT) are being actively studied. in this regard. HT restores altered insulin signaling pathway in cell model of AD [3] and prevents cognitive decline in a mouse model of Aβ deposition [4].

Emma Burgos-Ramos and colleagues evaluated the effects of HT on well-characterized mitochondrial dysfunction in a cellular model of AD. They reported an increase in the formation of new mitochondria after HT treatment (Figure 1), which was followed by higher mitochondrial fusion (Figure 2).

Figure 1. E ff and hydroxytyrosol (5 μM) on the markers of mitochondrial mass in 7PA2 cells treated for 4, 8 and 24 h. Control groups (C) are represented by empty bars and treated groups (HT) by solid bars. (A) Relative protein levels of citrate synthase (CS) and (C) peroxisome proliferator activated receptor γ coactivator la (PGC-1α). (B) Relative levels of PGC-1α mRNA and (D) of mitochondrial DNA. Data are means ± SEM of three di erent experiments performed in duplicate. DU, densitometry units. * P <0>
Figure 2. Densitometry from immunoblots derived from Western blot analysis of the relative levels of mitofusin 2 protein in 7PA2 cells treated with hydroxytyrosol for 4, 8 and 24 h. Control groups (C) are represented by empty bars and treated groups (HT) by solid bars. Data are percentages of the respective control means ± SEM from three different experiments performed in duplicate. DU, densitometry units. * P <0>

In addition, ATP concentrations were significantly increased after treatment with HT compared to controls (Table 1).

Table 1. Effect of HT treatment (5 µM) at 4, 8 and 24 hours on ATP levels (pmol / µl) in 7PA2 cells. Values ​​represent the mean ± SEM of three independent experiments were performed in duplicate. ** p <0>

Likewise, HT increased various markers of mitochondrial activity, such as ATP synthase and Aralar, proteins involved in obtaining energy.

In conclusion, this study suggests that HT can reverse the energy deficit of a cellular model of AD by potentiating mitochondrial activity. Because HT is offered as a dietary supplement or as a component of functional foods, future studies in appropriate animal models and - possibly - in humans are warranted to further investigate its potential neuroprotective actions in AD.

Emma Burgos-Ramos, PhD. Associate professor at the University of Castile-La Mancha (UCLM) exercises her teaching and investigative vocation at the Faculty of Environmental Sciences and Biochemistry from 2015. She began her research career by publishing 6 articles, all on Alzheimer's disease, in prestigious international neuroendocrinology journals. During her postdoctoral training, she obtained a prestigious contract from the Instituto Carlos III of Spain, which allowed her to publish 17 articles in international journals with a high impact factor on the pathogenesis of obesity and type 2 diabetes in the central nervous system and take advantage of two stays. at Universidad Clínica de Navarra and Ohio University, where she performed DNA microarray profiles and proteomic analyzes, respectively. She has also written several book chapters on metabolic syndrome and neurodegenerative diseases. In 2014, she joined the IMDEA Food Institute as a junior researcher where she began to study the effects of hydroxytyrosol on Alzheimer's disease and cognitive decline. Since then, Emma's main area of ​​research has focused on studying the effects of different nutraceuticals in the Mediterranean diet on neurodegenerative diseases. This line of research has generated 10 excellent articles so far.


  1. Guzman-Martinez L, Maccioni RB, Farias GA, Fuentes P, Navarrete LP. Biomarkers of Alzheimer's disease. Curr Alzheimer Res. 2019; 16 (6): 518-528.
  2. Skaper SD, Facci L, Zusso M, Giusti P. Synaptic plasticity, dementia and Alzheimer's disease. Drug targets for CNS neurological disorder. 2017; 16 (3): 220-233.
  3. Crespo MC, Tome-Carneiro J, Pintado C, Davalos A, Visioli F, Burgos-Ramos E. Hydroxytyrosol restores appropriate insulin signaling in an astrocytic model of Alzheimer's disease. Biofactors. 2017; 43 (4): 540-548.
  4. Nardiello P, Pantano D, Lapucci A, Stefani M, Casamenti F. Dietary supplementation with hydroxytyrosol improves brain pathology and restores cognitive functions in a mouse model of amyloid-beta deposition. J Alzheimers Dis. 2018; 63 (3): 1161-1172.

We would recommend either Wineworks Premium or Wineworks Superior as your first 30 Bottle Kit Wine. Both of these ranges are designed to produce a good quality wine that is ready to drink within 2-4 weeks but will benefit if left up to 6-8 weeks. Furthermore, they also have a great selection of wines to choose from.

If you’ve never made wine before or you simply don’t have any of the equipment or ingredients any longer then you could purchase one of our bundles. These bundles allie all the required equipment along with your prefered wine kit so that you can have everything delivered to your door and just get started. The Wineworks Superior Starter Bundles are a great choice if you want to keep the equipment budget down but still choose the quality of wine you’d like to go for. Whereas, the Wineworks Luxury Starter Bundles offer a better quality equipment pack and still let you choose from a great choice of wine kits.

The two most important critères of making wine are Cleanliness and Temperature. Firstly remember everything that comes into contact with the wine should be cleaned and sterilised ( see below ). Secondly maintain a constant temperature between 21-26°C ( 69-79°F ). It is much better to be on the cool side and constant than hot one minute and cold the next. Airing cupboards are definitely no, no’s. ( See below )

Clean and sterilise all equipment. Here’s a selection of Sterilisers you can use and if you not quite sure which steriliser to go for then you can take a look at our Beginners Wine Making Part 1 - Cleaning, Sterlising

Wineworks Superior wines : These usually take 10-15 days to ferment, and a further week to clear. Again the wine can be drunk immediately but we recommend ageing it 4 weeks but you can leave it up to 12 months. The time you will leave it will depend very much on your stocks. So get plenty built up. The reds benefit more than the whites with ageing. Certain kits ( see the list below ) are suited more to the experienced wine maker and take around 4 weeks to ferment and then left for a further 2 weeks. These products does really benefit from ageing. All the packs we list in this section require little ageing.

As it’s new to you it will probably take in all 2 hours for your first batch. However, once you are used to it 1 hour is about the maximum amount of time needed. We would also point out bar the bottling side; it takes just as long to make 6 bottles as it does to make 30 bottles, so we strongly recommend you make the larger quantity. After all 6 bottles doesn’t go very far as we said before !

From our experience it is much better to maintain a constant temperature than a fluctuating one. We suggest 21-26°C ( 69-79°F ), although if it is cooler than this, it is not a problem, it just takes slightly longer to ferment. If you can’t maintain this then we supply three different forms of heating equipment : Brew Belt / Heat BeltThis is a simple insulated electric cable that wraps round your conteneur and provides a gentle heat. It is very souple and extremely easy to use. Heat Tray ( 4 demi/5 Gallon Fermenter ) This is like a flat tray that provides a gentle continuous heat that goes under the fermenter. Immersion HeaterThis drops into the conteneur, through the bung and can be thermostatically controlled to maintain the exact temperature. Similar to a fish tank heater. All these can be added to our starter pack packages. See our scène showing the genres of heating equipment available for your fermentation.

It is important to clean

If you’ve made it this far, hopefully understanding a bit of what we’ve said, then you’ll want to know how much it will cost to get started ! As you may have noticed, we’ve put together a couple of equipment packs which include everything you need, and take the confusion out of buying. You can make your first 30 bottles of Wine for approximately £65. 00. That’s all in ( Equipment


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