Plant-Based Diets: Neuroprotective Powerhouses?

A plant-based diet has been shown to have neuroprotective effects. This is due to the presence of bioactive compounds, such as phenolic compounds, which are found in edible parts of plants. These compounds have been shown to have numerous beneficial effects due to their bioactivity.

Phenolic compounds have been reported to be found in edible parts of plants, but over the last few years, a large amount of research has focused on the phenolic richness that plant by-products possess, which sometimes even exceeds the content in the pulp. Thus, their possible application as an emergent neuroprotective technique could also be considered as an optimal strategy to revalorize these agricultural residues.

Phenolic compounds are considered a promising source of compounds for the treatment of age-related cognitive decline and the risk of developing neurodegeneration due to their antioxidant and anti-inflammatory properties. However, limitations related to their bioavailability and permeability through the blood–brain barrier (BBB) must be considered in the development of therapeutic applications with these compounds.

The neuroprotective role of agri-food by-product extracts has been scarcely studied. In this context, a comprehensive review of the state of the art in the application of by-products as neuroprotective agents against Alzheimer’s and Parkinson’s diseases is carried out in order to highlight the importance of their revalorization and to find new treatments to alleviate these neurodegenerative effects.

**Neuroinflammation** - Plant-based diets have been shown to reduce neuroinflammation, which is a common pathological hallmark of neurodegenerative disorders

Plant-based diets have been shown to reduce neuroinflammation, a common pathological hallmark of neurodegenerative disorders.

Neuroinflammation is a pathological process characterized by chronic inflammatory reactions in the central nervous system (CNS) that highly contributes to the development of a neurodegenerative state in the brain, mainly Alzheimer's disease (AD) and Parkinson's disease (PD).

Inflammatory responses triggered by brain protein aggregation are considered another important intracellular ROS source in the CNS. In AD, ROS presence oxidizes biomolecules such as proteins, DNA and carbohydrates, which are gradually accumulated in the cell over the years. Neurons, in an attempt to prolong cell life, promote Aβ secretion to sequester ROS, causing their oligomerization and aggregation. Aβ, in turn, is directly involved in ROS formation through peptidyl radicals, metal association or indirect activation of microglia. Therefore, high levels of ROS can be related to neurodegeneration, but they are not considered to be a direct initiator of neuropathies.

In PD, the formation of Lewy bodies also promotes the activation of non-neuronal cells, microglia and astrocytes. In addition, αS itself has direct proinflammatory activity. Oligomeric depositions of this peptide are phagocytosed by microglia, followed by their activation, and ROS and NO production, mostly produced by NADPH oxidase in activated microglia. Proinflammatory cascades then take place in the same way as explained above.

Plant-based diets have been shown to reduce neuroinflammation and are a potential neuroprotective research line. Phenolic bioactives have been reported to be found in edible parts of plants; however, over the last years, a large amount of research has focused on the phenolic richness that plant by-products possess, which sometimes even exceeds the content in the pulp. Thus, their possible application as an emergent neuroprotective technique could also be considered as an optimal strategy to revalorize these agricultural residues.

**Protein Aggregation** - Plant-based diets can prevent protein misfolding, aggregation and deposition, which are common in Alzheimer's and Parkinson's diseases

Plant-based diets are associated with a range of health benefits, including reduced risk of Alzheimer's and Parkinson's disease. These diets are thought to prevent protein misfolding, aggregation, and deposition, which are common in these diseases.

Protein misfolding is a common feature of degenerative diseases affecting the central nervous system or peripheral organs, and is characterised by the formation, deposition, and accumulation of toxic misfolded aggregates. Alzheimer's and Parkinson's diseases are two such diseases, and are associated with the aggregation of amyloid beta and alpha-synuclein proteins, respectively.

Plant-based diets are thought to prevent protein misfolding and aggregation by reducing oxidative stress and inflammation, which are strongly linked to these diseases. They may also reduce the toxicity of misfolded aggregates and promote their clearance.

Plant-based diets are also associated with lower levels of cholesterol, which can impair and ultimately block the protein degradation machinery, resulting in the collapse of the protein quality control system.

**Oxidative Stress** - Plant-based diets are rich in antioxidants, which can reduce oxidative stress, a key biological mechanism associated with neurodegeneration

Oxidative stress is a key biological mechanism associated with neurodegeneration. Plant-based diets are rich in antioxidants, which can reduce oxidative stress.

Antioxidants are compounds made in the body and found in food that help defend cells from free radicals, which can cause oxidative stress and increase the chance of developing various chronic diseases. Eating a diet rich in antioxidants increases blood antioxidant levels to reduce oxidative stress and disease risk.

Plant-based diets are generally higher in antioxidant content than animal-based and mixed food products, with median antioxidant values of 0.88, 0.10 and 0.31 mmol/100 g, respectively.

Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values.

Some of the most antioxidant-rich foods include:

• Spices and herbs
• Herbal/traditional plant medicine
• Vitamin and dietary supplements
• Berries and berry products
• Fruit and fruit juices
• Nuts and seeds
• Chocolate and sweets
• Vegetables and vegetable products
• Breakfast cereals
• Beverages
• Grains and grain products
• Dairy products, desserts and cakes
• Eggs, fats and oils
• Meat, poultry, fish and miscellaneous ingredients

**Mitochondrial Dysfunction** - Plant-based diets can improve mitochondrial biogenesis, influence mitochondrial fission and fusion, affect mitophagy, control mitochondrial quality and regulate mitochondrial functions such as ETC and ATP synthesis

Plant-based diets have been found to improve mitochondrial function and overall health. Mitochondria are often referred to as the "powerhouses" of cells, owing to their crucial role in adenosine triphosphate (ATP) production and cellular metabolism regulation.

Mitochondrial dysfunction is associated with obesity-related abnormalities and several diseases, including Alzheimer's and Parkinson's. Plant-based diets can positively influence mitochondrial health and, by extension, overall health.

Mitochondrial Biogenesis

Mitochondrial biogenesis refers to the growth and multiplication of mitochondria inside a cell. Calorie restriction, independent of weight loss, has been shown to increase mitochondrial biogenesis. Plant-based diets, such as the vegan diet, are often low in calories and can promote mitochondrial biogenesis. Additionally, ketogenic diets, which are typically high in healthy fats and low in carbohydrates, have been found to increase mitochondrial biogenesis. Plant-based diets rich in healthy fats, such as avocados, almonds, coconut oil, and olive oil, can contribute to this process.

Mitochondrial Fission and Fusion

Mitochondrial dynamics, including fission (division) and fusion (joining), play a crucial role in regulating mitochondrial energetics. Deficiency in proteins involved in mitochondrial fusion, such as Mfn2 and Opa1, can reduce respiration in various cell types. Plant-based diets rich in omega-3 polyunsaturated fatty acids, found in sources like walnuts, avocado, and olive oil, induce fusion processes and improve mitochondrial function.

Mitophagy

Mitophagy is a crucial process for cell survival, especially in neurons, as it involves the removal of dysfunctional mitochondria. Studies have found that the Mediterranean diet, rich in plant-based foods, can enhance mitophagy and promote healthy brain aging. Plant-based foods such as green pepper, cauliflower, broccoli, nuts, wheat germ, and mushrooms are excellent sources of spermidine, a compound believed to preserve high-order brain functions.

Mitochondrial Quality and Function

Mitochondria require a protective membrane composed of the fats we consume. Plant-based diets rich in healthy fats and phytonutrients, found in sources like extra-virgin olive oil, avocados, and walnuts, can nourish and protect mitochondria. Additionally, colorful vegetables provide phytonutrients and antioxidants, which help combat free radical damage and reduce oxidative stress.

Regulation of Mitochondrial Functions

Plant-based diets can influence the regulation of mitochondrial functions, such as the electron transport chain (ETC) and ATP synthesis. Diets rich in antioxidants, B vitamins, sulfur, fats, and magnesium, found abundantly in plant-based foods, can enhance mitochondrial energy production and cellular metabolism.

In summary, plant-based diets can positively impact mitochondrial health by improving biogenesis, influencing fission and fusion, enhancing mitophagy, protecting mitochondrial quality, and regulating mitochondrial functions like the ETC and ATP synthesis.

**Impaired Glutamatergic and Cholinergic Neurotransmissions** - Plant-based diets can inhibit enzymatic disorders that end in neurodegeneration, such as the overactivation of AChE and BChE (butyl cholinesterase)

Impaired Glutamatergic and Cholinergic Neurotransmissions are associated with Excitotoxicity, which is the excessive stimulation of neurons by neurotransmitters such as glutamate and acetylcholine. This can lead to neuronal cell death and is implicated in several neurological disorders, including Alzheimer's disease.

Plant-based diets can inhibit enzymatic disorders that lead to neurodegeneration, such as the overactivation of AChE and BChE. AChE is an enzyme that breaks down acetylcholine, a neurotransmitter that plays a role in memory and learning. BChE is also an enzyme that breaks down acetylcholine, but it is less specific than AChE.

Plant-based diets can inhibit the overactivation of AChE and BChE, which can help to prevent neurodegeneration and improve cognitive function.

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