Cellular stress activates endoplasmic-reticulum stress response characterized by cross-talk between the unfolded-protein response (UPR), autophagy, and mitochondrial-function. The outcome of this coordinated response is either restoration of cellular homeostasis or cell death. Aberrant regulation of mitophagy (mitochondria-specific autophagy) and the UPR results in mitochondrial-dysfunction, a recently acknowledged contributor to neurodegeneration. Elucidating mechanisms linking stress responses to neuronal function may lead to new treatments for psychiatric disorders and other neurodegeneration-related pathologies. The Research Topic will focus on these mechanisms.
Contributors will discuss, for example, how inhibiting autophagy by neuronal deletion of Atg7, an autophagy gene, is protective against neuronal death/hypoxia-ischemia-induced brain injury; introduce altered regulation of autophagy-regulating proteins in schizophrenia; describe genomic/ proteomic studies indicating that the mood-stabilizing drug lithium up-regulates the expression of genes/proteins required for autophagy and mitochondrial-function in mouse frontal-cortex - consistent with a role for autophagy in mood disorders; show that the mood-stabilizer valproate induces the UPR by up-regulating ceramide synthesis and provide a mechanistic link between mood disorder treatment and the UPR; and present evidence for cathepsin functional changes in epilepsy with potential involvement in mood disorders.
The potential that components of autophagy and of the UPR might become novel therapeutic targets for mood stabilization will also be discussed.
Cellular stress activates endoplasmic-reticulum stress response characterized by cross-talk between the unfolded-protein response (UPR), autophagy, and mitochondrial-function. The outcome of this coordinated response is either restoration of cellular homeostasis or cell death. Aberrant regulation of mitophagy (mitochondria-specific autophagy) and the UPR results in mitochondrial-dysfunction, a recently acknowledged contributor to neurodegeneration. Elucidating mechanisms linking stress responses to neuronal function may lead to new treatments for psychiatric disorders and other neurodegeneration-related pathologies. The Research Topic will focus on these mechanisms.
Contributors will discuss, for example, how inhibiting autophagy by neuronal deletion of Atg7, an autophagy gene, is protective against neuronal death/hypoxia-ischemia-induced brain injury; introduce altered regulation of autophagy-regulating proteins in schizophrenia; describe genomic/ proteomic studies indicating that the mood-stabilizing drug lithium up-regulates the expression of genes/proteins required for autophagy and mitochondrial-function in mouse frontal-cortex - consistent with a role for autophagy in mood disorders; show that the mood-stabilizer valproate induces the UPR by up-regulating ceramide synthesis and provide a mechanistic link between mood disorder treatment and the UPR; and present evidence for cathepsin functional changes in epilepsy with potential involvement in mood disorders.
The potential that components of autophagy and of the UPR might become novel therapeutic targets for mood stabilization will also be discussed.
