Could Fasting Help Control PD Symptoms?

This 2019 report in the National Library of Medicine (National Center for Biotechnology Information) looks at lifestyles and dietary habits associated with PD. A fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting the involvement of BDNF in FMD-mediated neuroprotection. The findings showed that FMD also inhibited neuroinflammation and modulated the shifts in gut microbiota composition.

Source: Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites – PubMed

Interaction of Mitochondria, a-Syn, and the Endo-lysosomal System

A 2019 study published in the International Journal of Molecular Sciences looked at the interaction of mitochondria, a-synuclein and the endo-lysosomal system. PD is characterized by dopaminergic neuronal loss and the alpha-synuclein-containing Lewy body inclusions in the substantia nigra. Genetic investigations have revealed evidence of the involvement of mitochondrial function, alpha-synuclein (α-syn) aggregation, and the endo-lysosomal system, in disease pathogenesis. Although familial parkinsonism makes up less than 10% of adult parkinsonism, the findings generated from genetic studies have enhanced the understanding of the neuron degeneration processes. These include mitochondrial dysfunction, disruption of network integrity, and α-syn accumulation; the functions of the proteasome and endo-lysosomal pathways in cellular degradation. Mitochondrial dysfunctions, endo-lysosomal disruptions, and α-syn aggregation mutually interact within neurons, while α-syn prion-like propagation may also be associated with PD in an inter-neuronal manner. Both mitochondria and endo-lysosomal dysfunction contribute to the development of α-syn pathology, however, the specific organelle playing the most important role might be decided by genetic and environmental factors. Most likely, a vicious cycle may develop once one system becomes dysfunctional. Further elucidation of the precise molecular mechanisms involved in the pathogenesis of PD may lead to the development of future therapeutic targets to treat PD.

Source: The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson’s Disease

Could α-Synuclein Inhibition be a Treatment for PD?

A 2020 publication in the MDPI journal, Biomolecules looks at targeting a-syn for PD therapeutics. PD is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy Bodies (cytoplasmic inclusions). The Lewy Bodies are clumps of protein that can build up and create problems in the brain. The Lewy Bodies contain the aggregated a-synuclein protein that can propagate throughout the brain. Many PD studies have looked at ways of inhibiting a-synuclein accumulation to ease PD symptoms. There are various approaches to a-syn inhibition and multiple clinical trials that examine the link between PD and a-syn, with the hope that a treatment may be found for PD using a-syn. Given the central role of α-syn in PD pathology and progression, α-syn met the criteria to be a tantalizing and evident therapeutic target for PD. Promising strategies include predominantly immunization, anti-aggregative molecules, and an increase in α-syn clearance.

Source: Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Ridding Cells of Harmful Protein Aggregates by Inducing Autophagy

This short, enlightening video clip is an extract from a FoundMyFitness interview with Dr. Guido Kroemer. PD is characterized by protein aggregation of a-synuclein and mitochondrial dysfunction, partly due to mitophagy failure. A recently proposed strategy in preventing (or perhaps treating) neurodegenerative diseases like PD is to starve the cells or use biochemical methods to induce general autophagy and thus help the cell rid itself of protein aggregates. Here Dr. Kroemer describes how mitophagy contributes to the pathophysiology of neurodegenerative diseases like PD and Alzheimer’s and how autophagy might mitigate these processes.

Neuronal Autophagy and the Predisposition for PD

A study by Dr. Yue published by the Michal J. Fox Foundation tested the hypothesis that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy predisposes to the pathogenesis of PD in dopamine neurons. This was done by establishing conditional knock-out mice in which an essential autophagy gene, Atg7, is deleted specifically in dopamine neurons. These pre-clinical models were used to investigate whether alpha-synuclein wildtype or PD-mutant A53T will be accumulated and deposited into Lewy body-like inclusions in the mutant dopamine neurons. In addition, they studied the effect of inactivation of autophagy on oxidative stress level, striatal dopamine content, and dopamine neuron degeneration. results suggest that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy may predispose dopamine neuron to PD-like pathology.

Source: Autophagy in Dopamine Neurons: Clearance of Alpha-synuclein and Neuroprotection

PD and Autophagy Impairment in Synucleinopathy

A 2019 study published by NCBI discusses the active participation of autophagy impairment in alpha-synuclein accumulation and propagation, as well as alpha-synuclein-independent neurodegenerative processes in the field of synucleinopathy. There is genetic and post-mortem evidence suggesting that autophagy is involved in synucleinopathies. Also, studies demonstrate the role of autophagy in the pathology of synucleinopathy. α-syn is mainly degraded by both macroautophagy and chaperone-mediated autophagy. Thus, autophagy defects induce intracellular α-syn accumulation, participating in its aggregative state towards the formation of α-syn-positive intracytoplasmic inclusions. Plus, autophagy defects also increase the α-syn secretion by the non-autophagic exosomal pathway, leading to increased cell-to-cell transmission of the protein, and thus the propagation of the α-syn-linked pathology in different brain regions of the CNS. However, autophagy defects also cause detriment effects in cellular homeostasis: (i) lysosomal impairment through structural or functional defects leads to accumulation of non-degraded products and increased production of ROS; (ii) decreased mitophagy leads to neuronal bioenergetic imbalance, and (iii) defective cargo trafficking impairs the addressing of vesicles to lysosomal clearance. There is increasing evidence that inducing the autophagy pathways (by natural, chemical, or genetic approaches), has become a relevant therapeutic approach to counteract the deleterious effects of autophagy impairment in synucleinopathy.

Source: Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein

Corynoxine, isolated from Uncaria rhynchophylla, promotes the clearance of alpha-synuclein via mTOR pathway [R].

use of Uncaria rhynchophylla, known as “Gou-teng” herb extract

buy uncaria-rhynchophylla:

buy Corynoxine:



mutant (A53T) α-synuclein exhibit impaired autonomic regulation of heart rate characterized by elevated resting heart rate

Mutations in α-synuclein cause some cases of familial PD. Several lines of transgenic mice that overexpress wild type or mutant human α-synuclein exhibit progressive accumulation of α-synuclein in neurons, motor dysfunction and death (). Mice expressing mutant (A53T) α-synuclein exhibit impaired autonomic regulation of heart rate characterized by elevated resting heart rate associated with accumulation of α-synuclein aggregates in the brainstem and reduced parasympa-thetic (cardiovagal) tone (). Maintenance of the α-synuclein mutant mice on ADF reversed the autonomic deficit, whereas a high fat diet exacerbated the autonomic deficit (). Consistent with the latter findings, a high fat diet hastened the onset of motor dysfunction and brainstem pathology in another line of α-synuclein mutant mice, which was associated with reduced activity of kinases known to be involved in neurotrophic factor signaling (). In addition to enhancement of neurotrophic factor/BDNF signaling, IF may counteract PD-related pathogenic processes by stimulating autophagy. Indeed, inhibition of mTOR with rapamycin, which stimulates autophagy, reduced oxidative stress and synaptic damage, and improved motor function in a α-synuclein accumulation-based mouse model of PD ().

full article intermittent fasting >> 

Longevity diet + Long fast (fmd), Intermintent fasting 5:2 16:8

vegetarian, no sugar, good oils, low protein, small fish

FMD see >>

see chapter 4 in the book

FMD –  file 28 longevity diet audiobook

research by longo regarding many conditions that benefit from periodic fasting

homemade FMD:

My Experience with the 5-Day Fasting Mimicking Diet

Dr Mattson research and recommendations 5:2 and 16:8

According to research conducted by neuroscientist Mark Mattson and others, cutting your energy intake by fasting several days a week might help your brain ward off neurodegenerative diseases like Alzheimer’s and Parkinson’s while at the same time improving memory and mood.

5:2 diet…every time you eat, glucose is stored in your liver as glycogen, which takes about 10 to 12 hours to be depleted. After the glycogen is used up, your body starts burning fats, which are converted to ketone bodies, acidic chemicals used by neurons as energy. Ketones promote positive changes in the structure of synapses important for learning, memory, and overall brain health. But if you eat three meals a day with snacks between, your body doesn’t have the chance to deplete the glycogen stores in your liver, and the ketones aren’t produced. Mattson says exercise can also get your body to lower its glycogen levels, and not coincidentally, exercise has been shown to have the same positive effects on brain health as fasting.

5:2 diet…when the brain is challenged by physical exertion, cognitive tasks, or caloric restriction, the body produces a protein called BDNF (brain-derived neurotrophic factor), which not only strengthens neural connections and increases the production of new neurons but can also have an anti-depressive effect.

see also Dr Fung on treating insulin resistance with low carb + fasting

IDM Program





Although autophagy fails to degrade large protein aggregates once they are formed in the cytoplasm, drug-induced activation of autophagy is effective in preventing aggregate deposition, indicating that autophagy significantly contributes to the clearance of aggregate-prone proteins. The pivotal role of autophagy in the clearance of aggregate-prone proteins has been confirmed by a deductive approach using a brain-specific autophagy-ablated mouse model.

Abstract –



Ketogenic Diet and LGIT diet vs plant based Atkins

plant based low carb diet -EcO Atkins…Some 31% of the calories in the diet came from plant proteins, 43% from vegetable oils, and 26% from carbs.

improve motor function full text
from the review:
The classic ketogenic therapy is based on a diet providing 90% of calories from long-chain fatty acids, a restricted protein portion (1 g/kg/day), and minimal carbohydrates. Traditionally, the diet is comprised of four parts fat, mainly LCTs, for one part carbohydrates and proteins. The ratio can be modified to 3:1, 2:1, or 1:1, respectively, similar to the modified Atkins diet (Kossoff et al., 2003). The MCTs diet is also proposed with 60% of calories from octanoate and decanoate that are more ketogenic than LCTs (Huttenlocher, 1976). The last alternative to a ketogenic therapy is the low glycemic index diet characterized by higher amounts of carbohydrates with low glycemic index (Coppola et al., 2011).

Autophagy works, see reference link in entry

blood lipids rise – see

Keto vs LGIT


Ketonemeter – see appendix