New Pieces for an Old Puzzle: Approaching Parkinson’s Disease from Translatable Animal Models, Gut Microbiota Modulation, and Lipidomics

Abstract

Parkinson’s disease (PD) is a severe neurodegenerative disease characterized by disabling motor alterations that are diagnosed at a relatively late stage in its development, and non-motor symptoms, including those affecting the gastrointestinal tract (mainly constipation), which start much earlier than the motor symptoms. Remarkably, current treatments only reduce motor symptoms, not without important drawbacks (relatively low efficiency and impactful side effects). Thus, new approaches are needed to halt PD progression and, possibly, to prevent its development, including new therapeutic strategies that target PD etiopathogeny and new biomarkers. Our aim was to review some of these new approaches. Although PD is complex and heterogeneous, compelling evidence suggests it might have a gastrointestinal origin, at least in a significant number of patients, and findings in recently developed animal models strongly support this hypothesis. Furthermore, the modulation of the gut microbiome, mainly through probiotics, is being tested to improve motor and non-motor symptoms and even to prevent PD. Finally, lipidomics has emerged as a useful tool to identify lipid biomarkers that may help analyze PD progression and treatment efficacy in a personalized manner, although, as of today, it has only scarcely been applied to monitor gut motility, dysbiosis, and probiotic effects in PD. Altogether, these new pieces should be helpful in solving the old puzzle of PD.

From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson’s Disease

“…Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disease, after Alzheimer's disease [1]. It affects approximately 6 million people worldwide and its prevalence is expected to increase in the next few years [1,2].…”

“…Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disease, after Alzheimer's disease [1]. It affects approximately 6 million people worldwide and its prevalence is expected to increase in the next few years [1,2]. In PD, an irreversible loss of dopaminergic neurons occurs in the substantia nigra and their corresponding axonal terminals in the striatum [1].…”

“…It affects approximately 6 million people worldwide and its prevalence is expected to increase in the next few years [1,2]. In PD, an irreversible loss of dopaminergic neurons occurs in the substantia nigra and their corresponding axonal terminals in the striatum [1]. Most cases of PD are likely the result of a combination of environmental and genetic factors [3].…”

“…Among the motor symptoms, bradykinesia, gait disturbances, tremors, rigidity, and speech deficits are the hallmarks of the disease. However, it is currently believed that PD begins many years before motor symptoms become clinically relevant [1], when some non-motor symptoms (depression, hyposmia (reduced sense of smell), cognitive impairment, sleep disorders, or constipation) may already occur [1,2].…”

Histological and electroencephalographic demonstration of probiotic effect for reduce of oxidative stress and apoptosis in experimental traumatic brain injury

“…[ 6 ] Consuming PB has some benefits, including improved lipid metabolism, reduced gut inflammation, and increased insulin sensitivity. [ 7 ] The gut microbiota play a role for many diseases such as neurodegenerative pathologies and also CNS injury according to previous research. [ 8 - 11 ]…”