Dear Colleagues,

Neurodegeneration refers to the progressive loss of structure or function of neurons, leading to a decline in cognitive and motor functions. Several diseases are characterized by neurodegeneration, and while each disease has its unique features, there are some common pathogenic mechanisms that contribute to the degeneration of neurons across different conditions. Here are some specific and common mechanisms underlying neurodegeneration:

(1) Protein Misfolding and Aggregation: Alzheimer's Disease (AD) (Amyloid-beta (Aβ) and tau proteins misfold and aggregate, forming plaques and neurofibrillary tangles); Parkinson's Disease (PD): (Alpha-synuclein misfolds and forms Lewy bodies. (2) Mitochondrial Dysfunction: Dysfunction in the energy-producing mitochondria is a common feature in many neurodegenerative diseases. Amyotrophic Lateral Sclerosis (ALS): Impaired mitochondrial function contributes to motor neuron degeneration. (3) Oxidative Stress: Free radicals and reactive oxygen species (ROS) damage cellular components, leading to neurodegeneration. Huntington's Disease (HD): Oxidative stress plays a role in the pathology of HD. (4) Inflammation: Chronic inflammation in the brain contributes to neuronal damage. Multiple Sclerosis (MS): Inflammatory processes result in demyelination and axonal damage. (5) Excitotoxicity: Overactivation of glutamate receptors leads to excessive influx of calcium ions, damaging neurons. Amyotrophic Lateral Sclerosis (ALS): Excitotoxicity contributes to motor neuron degeneration. (6) Genetic Factors: Mutations in specific genes contribute to the susceptibility or causation of neurodegenerative diseases. Frontotemporal Dementia (FTD): Mutations in genes such as C9orf72 are associated with FTD. (7) Impaired Autophagy and Proteasomal Dysfunction: Inefficient removal of damaged proteins and organelles contributes to the accumulation of toxic materials. Parkinson's Disease (PD): Impaired autophagy is implicated in the accumulation of alpha-synuclein. (8) Neuroinflammation: Activation of immune cells in the central nervous system contributes to neurodegeneration. Alzheimer's Disease (AD): Neuroinflammation is a characteristic feature of AD. (9) Vascular Dysfunction:

Impaired blood flow and vascular health contribute to neuronal damage. Vascular Dementia: Neurodegeneration is linked to vascular problems in the brain.

Understanding these common mechanisms helps researchers develop therapeutic strategies that target multiple diseases or pathways simultaneously. However, it is essential to consider the unique aspects of each neurodegenerative disorder for effective treatment approaches.

Therefore, this Special Issue invites the submission of research manuscripts, reviews, as well as short commentaries on topics related to the underlying mechanism and the role of specific or common signaling involved in the pathogenesis of neurodegenerative diseases. Submissions can cover reports from animal models to clinical studies in the field of neurodegenerative diseases.

Dr. Milena Atanasova
Prof. Dr. Jana Tchekalarova
Guest Editors

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• abnormal protein dynamics with misfolding
• defective degradation
• proteasomal dysfunction and aggregation
• often with actions and mutations of molecular chaperones
• oxidative stress (OS) and formation of free radicals/reactive oxygen species (ROS)