Abstract
Within neurodegenerative syndromes, Parkinson’s disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, Drosophila melanogaster (D. melanogaster), with leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain, provides mechanistic insights into corresponding human behaviour, possibly disclosing some physiopathologic features of PD in both genetic and sporadic forms. Moreover, several data support the boosting impact of innate and adaptive immunity pathways for driving the progression of PD. In this context, human dialyzable leukocyte extracts (DLE) have been extensively used to transfer antigen-specific information that influences the activity of various immune components, including inflammatory cytokines. Hence, the main goal of our study was to ascertain the therapeutic potential of DLE from male and female donors on D. melanogaster LRRK2 loss-of-function, as compared to D. melanogaster wild-type (WT), in terms of rescuing physiological parameters, such as motor and climbing activities, which are severely compromised in the mutant flies. Finally, in search of the anatomical structures responsible for restored functions in parkinsonian-like mutant flies, we found a topographical correlation between improvement of locomotor performances and an increased number of dopaminergic neurons in selective areas of LRRK2 mutant brains.
Highlights
Parkinson’s disease (PD) is a chronic, multifactorial and genetically heterogeneous neurodegenerative disorder with a tremendous epidemiology that accounts for 1–2% of incidences in the population over the age of 60 years [1], with a peak of 3.5% at ages 85–89 [2,3]
Data suggest a mild improvement in mutants at the highest concentration of fDLE (0.1%) and, surprisingly, at the lowest concentration (0.01%) of male dialyzable leukocyte extracts (mDLE) (Figures 1A and 2, respectively)
The WT flies treated with both mDLE and fDLE (0.01% and 0.1%) did not show any significant drug effects on motor activity compared to untreated controls (Figure 1A,B, Figures 2 and 3, respectively)
Summary
Parkinson’s disease (PD) is a chronic, multifactorial and genetically heterogeneous neurodegenerative disorder with a tremendous epidemiology that accounts for 1–2% of incidences in the population over the age of 60 years [1], with a peak of 3.5% at ages 85–89 [2,3] It is distinguished by integrated motor symptoms, namely, rigidity, bradykinesia, resting tremors and postural instability. Brain Sci. 2020, 10, 45 juvenile and late onset [9] Among these [10], the leucine-rich repeat kinase 2 (LRRK2) gene contains multiindependent domains that are widely expressed within different brain areas, such as the cortex, striatum, hippocampus and cerebellum, and in dopaminergic neurons of the substantia nigra [11,12,13,14]
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