Melissa Vos

• PhD
• PostDoc Position at University of Lübeck

Parkinson’s disease (PD) is a neurodegenerative disorder with a high variability of age at onset, disease severity, and progression. This suggests that other factors, including genetic, environmental, or biological factors, are at play in PD. The loss of PINK1 causes a recessive form of PD and is typically fully penetrant; however, it features a wi...

Parkinson’s disease (PD) is a neurodegenerative disorder with a high variability of age at onset, disease severity, and progression. This suggests that other factors, including genetic, environ-mental, or biological factors, are at play in PD. Loss of PINK1 causes a recessive form of PD and is typically fully penetrant; however, it features a wide...

Despite being a major component of Lewy bodies and Lewy neurites, pathogenic variants in the gene encoding alpha-Synuclein (α-Syn) are rare. To date, only four missense variants in the SNCA gene, encoding α-Syn have unequivocally been shown to be disease-causing. We here describe a Parkinson´s disease patient with early cognitive decline carrying a...

Sphingolipids, including the basic ceramide, are a subset of bioactive lipids that consist of many different species. Sphingolipids are indispensable for proper neuronal function, and an increasing number of studies have emerged on the complexity and importance of these lipids in (almost) all biological processes. These include regulation of mitoch...

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is a rare disease that exhibits brain modifications and motor dysfunctions in early childhood. The condition is caused by a homozygous or compound heterozygous mutation in fatty acid 2 hydroxylase (FA2H), whose encoded protein synthesizes 2-hydroxysphingolipids and 2-hydroxyglycosphingolipi...

Beta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA) caused by loss-of-function variants in WDR45. The underlying mechanism of iron accumulation in WDR45 deficiency remains elusive. We established a primary skin fibroblast culture of a new BPAN patient with a missense varia...

The etiology and progression of Parkinson’s Disease (PD), the second most prevalent neurological disorder, have been widely investigated for several decades; however, a cure is still lacking. Despite the development of several neurotoxins and animal models to study this rather heterogeneous disease, a complete recapitulation of the neurophysiology...

Mitophagy and energy production are two functionalities in which PINK1 plays a key role. Loss of PINK1 is one of the genetic causes of Parkinson disease (PD), suggesting both processes are important in PD pathogenesis. Nonetheless, it remains unclear whether these processes are connected or independent of one another. Sphingolipids, including ceram...

Neurodegenerative diseases are incurable diseases of the nervous system that lead to a progressive loss of brain areas and neuronal subtypes, which is associated with an increase in symptoms that can be linked to the affected brain areas. The key findings that appear in many neurodegenerative diseases are deposits of proteins and the damage of mito...

Significance Ceramide accumulates in Parkinson’s disease–related PINK1 deficiency to initiate ceramide-mediated mitophagy as an alternative pathway to overcome defective PINK1-related mitophagy and the concomitant increased requirements for mitochondrial clearance. Increased ceramide levels negatively correlate with β-oxidation and thus decrease ef...

Parkinson’s disease (PD) is a complex neurodegenerative disorder that is currently incurable. As a consequence of an incomplete understanding of the etiology of the disease, therapeutic strategies mainly focus on symptomatic treatment. Even though the majority of PD cases remain idiopathic (~90%), several genes have been identified to be causative...

Background: Despite rapid advances in research on Parkinson's disease (PD), in particular in the elucidation of genetic contributions, no disease-modifying therapy has become available to date. Objectives: In the proposed project, we aim to investigate the potential effects of vitamin K2 (long-chain menaquinone 7, MK-7) in genetically determined PD...

De novo variants represent a significant cause of neurodevelopmental delay and intellectual disability. A genetic basis can be identified in only half of individuals who have neurodevelopmental disorders (NDDs); this indicates that additional causes need to be elucidated. We compared the frequency of de novo variants in patient-parent trios with (n...

PINK1 is mutated in Parkinson's disease (PD), and mutations cause mitochondrial defects that include inefficient electron transport between complex I and ubiquinone. Neurodegeneration is also connected to changes in lipid homeostasis, but how these are related to PINK1-induced mitochondrial dysfunction is unknown. Based on an unbiased genetic scree...

Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by the loss of dopaminergic neurons. This loss of dopaminergic neurons is the pathological hallmark of the disease that results in the characteristic motor syndrome. Restoration of dopamine levels is the basis of current therapy; however, this does not tackle the cause of...

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra, as well as in other brain areas. The currently available dopamine replacement therapy provides merely symptomatic benefit and is ineffective because habituation and side effects arise relatively qu...

Mitochondrial electron transport chain (ETC) defects are observed in Parkinson's disease (PD) patients and in PD fly- and mouse-models; however it remains to be tested if acute improvement of ETC function alleviates PD-relevant defects. We tested the hypothesis that 808 nm infrared light that effectively penetrates tissues rescues pink1 mutants. We...

The prevalence of intellectual disability is around 3%; however, the etiology of the disease remains unclear in most cases. We identified a series of patients with X-linked intellectual disability presenting mutations in the Rad6a (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme. Drosophila deficient for dRad6 display defective sy...

(A) Quantification of the mitochondrial aggregate number per DA neurons in PPM3 cluster. Data collected from 5 neurons per brain in at least 10 brains. Significantly different * from control, ° from pink1B9, °° ple>NDUFA8RNAi, ns not significantly different. One-way ANOVA, post hoc Dunnett p<0.01. Data are shown as Mean ± SEM. (B) Flight ability of...

(A) Schematic representation of the acon gene. C→A in acon1 is cytosine adenine transition that results in a STOP codon; The insertion site of Mi{ET1}AconMB09176 is indicated. (B) complementation test table of different heteroallelic combinations, “genomic” indicates a genomic fragment containing the wild type acon locus and da>uasAcon indicates fl...

It is estimated that the human mitochondrial proteome consists of 1,000-1,500 distinct proteins. The majority of these support the various biochemical pathways that are active in these organelles. Individuals with an oxidative phosphorylation disorder of unknown cause provide a unique opportunity to identify novel genes implicated in mitochondrial...

The PTEN-induced kinase 1 (PINK1) is a mitochondrial kinase, and pink1 mutations cause early onset Parkinson's disease (PD) in humans. Loss of pink1 in Drosophila leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance of dysfunctional mitochondria...

Keeping Mitochondria in the Pink Pink1 is a mitochondrial kinase, and loss of Pink1 function in flies and mice results in the accumulation of inefficient mitochondria. In a screen for modifiers of the Parkinson-associated gene, pink1 , Vos et al. (p. 1306 , published online 10 May; see the Perspective by Bhalerao and Clandinin ) identified the frui...

Pink1 is a mitochondrial kinase involved in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery. Pink1 loss also affects the enzymatic activity of isolated Complex I of the electron transport chain (ETC); however, the primary defect...

Expression of AOX is benign. (A) Quantification of flight in w; UAS-AOX/+; da-Gal4/+ and in w; da-Gal4/+ controls. Data represent the average +/− SEM of n = 6 (5 flies per independent test). Student's t-test: ns = non-significant. (B) Quantification of indentations in w; UAS-AOX/+; da-Gal4/+ and in w; da-Gal4/+ controls. Data represent the average...

Primers used for Q-RT-PCR and PCR from genomic DNA. List of primers used for Q-RT-PCR and of primers used for PCR of genomic DNA. (DOC)

Supplemental methods. (DOC)

Expression of NDI1 rescues pink1 mutant defects in neurotransmitter release. (A) Quantification of the amplitude of excitatory junctional potentials measured in 2 mM external calcium in pink1RV controls (w pink1RV; da-Gal4/+), in larvae expressing NDI1 (w; UAS-NDI1/+; da-Gal4/+), in pink1B9 mutants (w pink1B9; da-Gal4/+) and in pink1B9 mutants expr...

Cell types rich in mitochondria, including neurons, display a high energy demand and a need for calcium buffering. The importance of mitochondria for proper neuronal function is stressed by the occurrence of neurological defects in patients suffering from a great variety of diseases caused by mutations in mitochondrial genes. Genetic and pharmacolo...

Phylogenetic analysis of novel dolphin (Tursiops truncatus) papillomavirus sequences, TtPV1, -2, and -3, indicates that the early and late protein coding regions of their genomes differ in evolutionary history. Sliding window bootscan analysis showed a significant a change in phylogenetic clustering, in which the grouped sequences of TtPV1 and -3 m...