Attenuation of dopamine transporter activity by α-synuclein

  title={Attenuation of dopamine transporter activity by $\alpha$-synuclein},
  author={Christophe Wersinger and Anita Sidhu},
  journal={Neuroscience Letters},

α-Synuclein Stimulates a Dopamine Transporter-dependent Chloride Current and Modulates the Activity of the Transporter*

Findings are consistent with the interpretation that DAT/α-synuclein interaction at the cell surface results in a DAT-dependent, Na+-insensitive, Cl-sensitive inward current with a decrease in substrate uptake, suggesting that Dat/ α-syn nuclein interaction can modulate dopamine transmission and thus neuronal function.

Inhibition of Vesicular Monoamine Transporter-2 Activity in α-Synuclein Stably Transfected SH-SY5Y Cells

It is suggested that Up-regulated α-synuclein expression inhibits the activity of vesicular monoamine transporter-2, thereby interrupting dopamine homeostasis and resulting in dopaminergic neuron injury in Parkinson’s disease.

Modulation of dopamine transporter function by α‐synuclein is altered by impairment of cell adhesion and by induction of oxidative stress

A novel normative role for α‐synuclein is suggested in regulating DA synaptic availability and homeostasis, which is relevant to the pathophysiology of PD.

Attenuation of the norepinephrine transporter activity and trafficking via interactions with α‐synuclein

It is proposed that a primary physiological role of α‐Syn may be to regulate the homeostasis of monoamines in synapses, through modulatory interactions of the protein with monoaminergic transporters.

α-Synuclein and dopamine metabolism

The regulatory effect of α-Syn on dopamine metabolism is likely to tone down the amount of cytoplasmic dopamine at nerve terminals, thereby limiting its conversion to highly reactive oxidative molecules.

Silencing α-Synuclein Gene Expression Enhances Tyrosine Hydroxylase Activity in MN9D Cells

The data show that TH activity and DA biosynthesis were enhanced by down-regulation of α-synuclein, suggesting that α- synuclein may act as a negative regulator of cytosolic DA.

Striatal Dopamine Transporter Function Is Facilitated by Converging Biology of α-Synuclein and Cholesterol

Data indicate that human α-synuclein in a mouse model of PD promotes striatal DAT function, in a manner supported by extracellular cholesterol, suggesting converging biology of α- synuclein and cholesterol that regulates DATfunction and could impact DA function and PD pathophysiology.



Direct binding and functional coupling of α-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis.

It is reported that α-synuclein complexes with the presynaptic human dopamine transporter (hDAT) in both neurons and cotransfected cells through the direct binding of the non-Aβ amyloid component of α- synuclein to the carboxyl-terminal tail of the hDAT accelerate dopamine-induced apoptosis.

α‐Synuclein and Parkinson's disease

Findings to date suggest that α‐syn‐based models represent a paradigm, which is closest to the human pathology, which has hindered the development of models to study Parkinson's disease.

Alpha-synuclein and Parkinson's disease

Although little has been learned about its normal function, α-synuclein appears to interact with a variety of proteins and membrane phospholipids, and may therefore participate in a number of signaling pathways and play a role in regulating cell differentiation, synaptic plasticity, cell survival, and dopaminergic neurotransmission.

Degradation of α-Synuclein by Proteasome*

The degradation of both recombinant proteins and endogenous α-synuclein in these cells was blocked by the selective proteasome inhibitor β-lactone, indicating that both wild-type and A53T mutant α- synuclein are degraded by the ubiquitin-proteasome pathway.

Physiology and Pathophysiology of α‐Synuclein: Cell Culture and Transgenic Animal Models Based on a Parkinson's Disease‐associated Protein

Abstract: The 15–20 kDa synuclein (SYN) phosphoproteins are abundantly expressed in nervous tissue. Members of the family include α‐ and β‐SYN, and the more distantly related γ‐SYN and synoretin. SYN

α-Synuclein Protects against Oxidative Stress via Inactivation of the c-Jun N-terminal Kinase Stress-signaling Pathway in Neuronal Cells*

Results suggest that increased α-synuclein expression might protect cells from oxidative stress by inactivation of JNK via increased expression of JIP-1b/IB1, which may play a mutual role in the neuronal response to injury and neurodegeneration.

Synucleins in synaptic plasticity and neurodegenerative disorders.

A hypothesis whereby synuclein supports localized, experience‐dependent turnover of synaptic membranes may be important for lifelong learning and memory functions and may be especially vulnerable to disruption in aging‐associated neurodegenerative diseases is outlined.