Premium Nahrungsergänzungsmittel | artgerecht

Proteostasis – Meaning, Function and Diseases

Proteostasis describes the cellular balance of all proteins from synthesis to degradation. Disruptions are linked to aging and serious diseases.

Regular tips about health Regular tips about health

Things worth knowing about "Proteostasis"

Proteostasis describes the cellular balance of all proteins from synthesis to degradation. Disruptions are linked to aging and serious diseases.

What Is Proteostasis?

The term proteostasis is a combination of the words “protein” and “homeostasis.” It describes the dynamic equilibrium of all proteins within a cell or organism. Proteins are the functional building blocks of life: they drive metabolic processes, form structural components, transport molecules, and regulate signaling pathways. For cells to function properly, proteins must be present in the right quantity, the correct three-dimensional shape, and at the right location.

Proteostasis encompasses all processes that ensure proteins are correctly produced (synthesis), folded into their functional structure (folding), repaired when necessary (maturation and quality control), and ultimately broken down (degradation). This interconnected system is referred to as the proteostasis network.

Components of the Proteostasis Network

Molecular Chaperones

Chaperones are helper proteins that assist newly synthesized or stress-unfolded proteins in achieving their correct three-dimensional shape. They prevent proteins from clumping together (aggregation) and promote accurate folding. Well-known chaperones include the heat shock proteins (HSPs) such as HSP70 and HSP90, which are especially activated during cellular stress.

Ubiquitin-Proteasome System (UPS)

The ubiquitin-proteasome system is the primary pathway for the targeted degradation of misfolded or damaged proteins. Proteins that are no longer needed or are incorrectly folded are tagged with the small protein ubiquitin. This signal directs them to the proteasome, a cellular degradation complex that breaks proteins down into their amino acid building blocks.

Autophagy

Autophagy (from the Greek meaning “self-eating”) is another important degradation pathway in which larger protein aggregates or damaged organelles are enclosed in specialized membrane vesicles and subsequently broken down. It plays a crucial role in clearing the cell of toxic accumulations.

Endoplasmic Reticulum and Unfolded Protein Response (UPR)

Much of protein folding occurs in the endoplasmic reticulum (ER). When too many misfolded proteins accumulate there, the cell activates a stress response known as the Unfolded Protein Response (UPR). This reaction attempts to restore equilibrium by reducing protein synthesis, increasing folding capacity, and accelerating the degradation of misfolded proteins.

Relevance to Health and Disease

An intact proteostasis network is essential for good health. When this balance is disrupted, misfolded or aggregated proteins can accumulate and become toxic to the cell. Proteostasis disruptions are associated with a wide range of diseases, including:

Neurodegenerative diseases such as Alzheimer disease (accumulation of amyloid-beta and tau protein), Parkinson disease (alpha-synuclein aggregates), and Huntington disease (mutant huntingtin protein)
Type 2 diabetes (amyloid deposition in the pancreas)
Amyloidosis (systemic deposition of misfolded proteins in organs)
Cystic fibrosis (caused by misfolding of the CFTR protein)
Cancer (altered proteostasis supports uncontrolled cell growth)

Proteostasis and Aging

As organisms age, the efficiency of the proteostasis network declines. The activity of chaperones and proteasomes decreases, while the frequency of misfolded proteins increases. This age-related decline in proteostasis is considered a central mechanism of biological aging and a key factor in the development of age-related diseases.

Therapeutic Approaches

Targeted modulation of proteostasis is a promising area of modern medical research. Several strategies are being investigated:

Proteasome inhibitors: Drugs such as bortezomib are already used in certain cancers to block protein degradation and induce tumor cell death.
Chaperone therapy: Pharmacological chaperones can be used in certain conditions such as cystic fibrosis to stabilize misfolded proteins.
Autophagy modulators: Substances that stimulate autophagy (e.g., rapamycin) are being investigated for their potential in treating neurodegenerative diseases.
Lifestyle interventions: Physical exercise, caloric restriction, and fasting can strengthen the proteostasis network and are being intensively studied in aging research.

References

Balch, W. E. et al. (2008): Adapting Proteostasis for Disease Intervention. Science, 319(5865), 916–919. DOI: 10.1126/science.1141448
Hipp, M. S., Kasturi, P. & Hartl, F. U. (2019): The proteostasis network and its decline in ageing. Nature Reviews Molecular Cell Biology, 20, 421–435. DOI: 10.1038/s41580-019-0101-y
Bhattacharyya, S. et al. (2014): Regulated protein aggregation: stress granules and neurodegeneration. Trends in Neurosciences, 37(10), 583–590. DOI: 10.1016/j.tins.2014.08.003

Building Blocks for a Healthy Life

As an integrated manufacturer, we develop & produce evidence-based, patented, and non-patented formulations. We work exclusively with plant and natural extracts according to the strictest purity & quality standards.
The combination of science & modern technology with the laws of nature creates solutions consistently tailored to humans – for the highest good: health.